(Circulation. 1995;92:2135-2141.)
© 1995 American Heart Association, Inc.
Articles |
From the Vascular Medicine and Atherosclerosis Unit, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (S.B.W., D.E.L., P.B., M.A.C.), and the Division of General Internal Medicine, Department of Medicine, University Hospital Nijmegen, the Netherlands (P.S., G.A.R.).
Correspondence to Mark A. Creager, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.
| Abstract |
|---|
|
|
|---|
Methods and Results Venous occlusion plethysmography was used to assess the forearm blood flow (FBF) responses to graded intra-arterial infusions of adenosine (1.5 to 500 µg/min). Dose-response curves were constructed before and during intra-arterial infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) (2 mg/min, n=6) or vehicle (n=6). Before infusion of L-NMMA, adenosine caused a dose-dependent increase in FBF from 2.3 to 15.9 mL · min-1 · dL-1. During concurrent infusion of L-NMMA, adenosine increased FBF from 1.7 to 10.0 mL · min-1 · dL-1, and this change from baseline was significantly reduced compared with that before L-NMMA (P<.05). L-NMMA also attenuated the FBF response to adenosine when the basal constrictor effect of L-NMMA was prevented by coinfusion of the NO donor sodium nitroprusside (n=6, P<.01). In contrast, L-NMMA did not affect the FBF response to intra-arterial infusion of the endothelium-independent vasodilator verapamil (from 2.0 to 13.9 mL · min-1 · dL-1 before L-NMMA and from 1.3 to 13.6 mL · min-1 · dL-1 during L-NMMA; n=6, P=NS). The second objective of this study was to determine whether the adenosine-induced release of NO is mediated by activation of endothelial potassium channels, putatively coupled to adenosine receptors. Thus, the FBF response to adenosine was measured before and during infusion of the ATP-dependent potassium channel blocker tolbutamide (1 mg/min, n=6), or the potassium channel blocker quinidine (0.5 mg/min, n=6). The adenosine-mediated increments in FBF were not attenuated by either potassium channel blocker.
Conclusions Adenosine-induced vasodilation in humans is mediated, at least in part, by endothelial release of NO. The transducing mechanism of this phenomenon is not known, but it does not appear to involve the activation of either ATP-dependent or quinidine-sensitive potassium channels.
Key Words: nitric oxide vasodilation endothelium adenosine
| Introduction |
|---|
|
|
|---|
Several potential mechanisms could mediate the
endothelial release of NO during adenosine
administration. Stimulation of endothelial
adenosine receptors may mobilize calcium and thereby
activate endothelial NO
synthase.10 Adenosine A1-receptors
have been demonstrated to be coupled to ATP-dependent potassium
channels by guanine nucleotide binding proteins, in
particular by the G
i proteins.11 The
G
i proteins can mobilize calcium by stimulating
phosphoinositide-specific phospholipase C activity,
causing hydrolysis of phosphatidylinositol
4,5-diphosphate.12 Also, adenosine can stimulate
the endothelial influx of calcium and thereby NO
synthesis by activating ATP-dependent potassium channels and
hyperpolarizing endothelial cells.13 14 In
addition, potassium channel activation and NO release can be triggered
nonspecifically by increments in shear stress related to the raised
flow.15
In the present study we evaluated whether the endothelial release of NO plays an important role in the vasodilating effects of adenosine in humans and, if it does, whether the aforementioned potential mechanisms are involved in that NO release. Human data on this subject are especially important given the large interspecies differences in endothelial pharmacology.16 To address these questions, the effects of adenosine were assessed in vivo by use of the perfused forearm technique, both before and during blockade of the production of NO by the NO synthase inhibitor L-NMMA and before and during blockade of potassium channels by the sulfonylurea derivative tolbutamide and the antiarrhythmic drug quinidine. These studies, as well as appropriate control experiments, allow us to conclude that the vascular effects of adenosine in humans are based, at least in part, on the endothelial release of NO. This adenosine-induced release of NO is not mediated by activation of ATP-dependent potassium channels or by quinidine-sensitive potassium channels.
| Methods |
|---|
|
|
|---|
Each subject participated in one experiment of approximately 4 hours' duration. The experiments were performed in a quiet, temperature-controlled room (22°C). The participants were all asked to abstain from food, alcohol, and caffeine for at least 12 hours before the test. Because caffeine acts as a potent adenosine receptor antagonist in the human cardiovascular system,21 we measured plasma caffeine levels at the time of the test to ensure compliance with respect to the abstinence recommendations. The subjects remained in the supine position throughout the test. After each subject's arrival in the laboratory, the left brachial artery was cannulated under local anesthesia with a 20-gauge catheter, which was used for intra-arterial drug infusion as well as for blood pressure monitoring (Gould Inc). Drugs were delivered with an automatic syringe infusion pump (Harvard Apparatus).
FBF recordings were started after an equilibration period of at least 40 minutes. FBF was measured in each arm by venous occlusion mercury-in-Silastic strain-gauge plethysmography (Hokanson EC4, D.E. Hokanson) as previously described.19 Both arms rested in slings at heart level, with the forearms slightly elevated to ensure a sufficient venous return. To be sure that FBF recordings referred predominantly to the forearm skeletal muscle circulation, the hand circulation was occluded during all FBF recordings by a wrist cuff inflated 100 mm Hg above the systolic blood pressure.22
Assessment of the Role of NO in the Vasodilator Response to
Adenosine and Verapamil
In the first subgroup of six subjects, the vasodilator response
to increasing dosages of adenosine was investigated. Baseline
measurements were taken during infusion of placebo (glucose 5%) into
the brachial artery. Adenosine was then infused
intra-arterially in six increasing dosages for 4
minutes per dose (adenosine dosages were 1.5, 5, 15, 50, 150,
and 500 µg/min). Measurements were performed during the last 2
minutes of each infusion. After an equilibration interval of 60 minutes
in which the FBF was allowed to return towards baseline levels, new
baseline recordings were obtained during placebo infusion.
Subsequently, infusion of L-NMMA into the brachial artery was started
at a dose of 2 mg/min. After 15 minutes of the L-NMMA-infusion alone,
hemodynamic measurements were taken to evaluate the
vasoactive effects of L-NMMA. Thereafter, the six increasing
adenosine dosages were again administered and coinfused with
L-NMMA. The total duration of L-NMMA infusion was approximately 40
minutes. In an additional series of three subjects, we verified that
infusion of L-NMMA at 2 mg/min for 40 minutes induced a
steady-state vasoconstrictor response that did not progress over
time.
In the next group of six subjects, similar experiments were performed with a similar time schedule and drug dosages of adenosine and L-NMMA, but with these experiments the L-NMMA infusion was accompanied by a low intra-arterial dose of the NO donor SNP. Previous studies have shown that L-NMMA infusion induces a vasoconstrictor response in the forearm vascular bed by inhibiting the basal release of NO from the endothelium.23 From a methodological viewpoint, this change in baseline could complicate the interpretation of the results, given that the baseline vascular resistance is an important determinant of the response to a vasodilator stimulus24 and that the achieved concentrations of adenosine are proportionally higher in a vasoconstricted state. From pilot studies, we determined that an intra-arterial dose of SNP of 0.2 µg/min was appropriate to counteract the vasoconstrictor response to L-NMMA. Therefore, this dose of SNP was coinfused with L-NMMA. The "clamping" of the NO-mediated vascular tone by the concomitant infusion of L-NMMA and SNP has recently been shown to be a useful approach in animal experiments on this subject.25
An additional six subjects were studied for reasons of time control. The same time schedule was used as in the other adenosine experiments; however, the second dose-response measurement was performed in the presence of placebo instead of active drug. This study was done to ensure that the forearm vasodilator response to adenosine did not change over the 4-hour experimental session.
In theory, NO release from the endothelium may have been triggered nonspecifically by the adenosine-induced increase of shear stress resulting from the high FBFs. To evaluate this nonspecific stimulus of NO release, we measured FBF responses to the endothelium-independent calcium entry blocker verapamil before and after L-NMMA (2 mg/min) in another six subjects. Verapamil was used in four dose-steps of 5 minutes each (10, 30, 100, 300 µg/min). Because verapamil has a longer half-life than adenosine, we waited for 90 minutes to wash out the drug after the first series of verapamil infusion. Apart from these details, the time schedule was similar to that used in the previous experiments.
Assessment of the Role of Potassium Channel Activation in the
Vasodilator Response to Adenosine
It recently was shown that adenosine receptors are
coupled to ATP-dependent potassium channels.11 These
channels can be blocked specifically by sulfonylurea derivatives, not
only in the pancreatic ß cells but also at the level of the vessel
wall.26 Therefore, adenosine dose-response
studies were performed in a fifth group of six volunteers before and
during the intrabrachial infusion of tolbutamide (1 mg/min). The
infusion of tolbutamide started 15 minutes before the first
adenosine dose. Because systemic dosages of tolbutamide may
induce hypoglycemia by stimulating insulin release and because insulin
increases skeletal muscle blood flow and alters vascular responsiveness
to drugs in the forearm model,27 28 arterial
blood samples for glucose and insulin were taken just before and after
tolbutamide infusion to demonstrate that no systemic effects occurred
at this low dose.
In an additional six healthy volunteers, the vascular response to adenosine was assessed before and during the intra-arterial infusion of 0.5 mg/min quinidine. Studies have shown by use of the patch-clamp technique that quinidine blocks several types of potassium channels,29 30 31 32 33 including those activated by adenosine. To limit the cumulative dose of quinidine in healthy volunteers, we used only the four highest adenosine dosages (instead of all six) in these subjects. Measurements of FBF and subsequent administration of the four adenosine dosages were started after 10 minutes of quinidine infusion, and the total infusion time of quinidine was restricted to 30 minutes (cumulative dose, 15 mg).
Drugs
Adenosine was prepared for each experiment by dilution
of Adenocard vials (6 mg per 2 mL, Fujisawa Pharmaceutical Co) in
saline.
NG-monomethyl-L-arginine
acetate, purchased from Calbiochem, was diluted in glucose 5% just
before the experiments. SNP was purchased from Elkins-Sinn, Inc.
Protected from light, it was dissolved in glucose 5% just before
administration. Verapamil HCl (American Reagent
Laboratories Inc) was diluted with glucose 5%. For the tolbutamide
experiments, sterile tolbutamide sodium (Orinase
Diagnostic, The Upjohn Co) was dissolved in saline (NaCl
0.9%). For the quinidine studies, we used quinidine gluconate vials
(Eli Lilly) of 800 mg/10 mL diluted in glucose 5%. Depending on the
experiment, glucose 5% or saline was used as placebo infusion. All
drugs and placebo infusions were administered at the same infusion rate
of 0.4 mL/min.
Statistics and Calculations
The effects of adenosine were analyzed by
comparison of the hemodynamic variables at baseline
and at the six dosage levels by one-way ANOVA with repeated
measures. Post hoc comparisons between the different dosages were made
by Scheffé's F tests. The paired t test
was used for the assessment of the effects of L-NMMA, tolbutamide, or
quinidine on baseline parameters. To evaluate the effect of
the intervention (NO synthase blockade, potassium channel blockade) on
the adenosine or verapamil responses, two-way
repeated-measures ANOVA was performed on the changes from baseline.
Because the mean arterial blood pressure was not affected
by either drug infusion (see "Results"), FBF changes were assumed
to represent changes in forearm vascular tone. Differences were
considered to be statistically significant at P<.05
(two-tailed). All results are presented as mean±SEM unless
otherwise indicated.
| Results |
|---|
|
|
|---|
Plasma caffeine levels could not be detected in 20 of 23 subjects in whom it was measured (lower limit of assay, 0.5 mg/L). In the remaining three subjects, caffeine concentration ranged from 1.8 to 4.0 mg/L. Despite detectable caffeine levels in these three subjects, each showed a vasodilator response to adenosine that was comparable to that observed in the others, justifying inclusion of their data in the results. Moreover, statistical analysis after exclusion of these subjects did not affect the outcome of the findings.
Vasoconstrictor Response to L-NMMA
To assess the effect of L-NMMA on basal FBF, the data from six
L-NMMAadenosine experiments, three L-NMMA time-control
experiments, and six L-NMMAverapamil experiments were
pooled. After 15 minutes of intra-arterial L-NMMA
infusion, FBF decreased significantly from 2.1±0.2 to 1.5±0.1
mL · min-1 · dL-1 (n=15, paired
t test: P<.01). In contrast, the FBF of the
contralateral noninfused arm remained constant during this infusion
(1.8±0.1 before and 1.8±0.1
mL · min-1 · dL-1 during L-NMMA
infusion). Moreover, L-NMMA infusion did not change the mean
arterial blood pressure (81.3±2.3 versus 79.1±2.7 mm Hg,
P=NS) or heart rate (56.1±2.2 versus 54.9±2.1 beats per
minute, P=NS), indicating that local L-NMMA infusion did not
affect systemic hemodynamics. In the three subjects in
whom L-NMMA was the only drug given, the FBF fell from 1.8±0.3
mL · min-1 · dL-1 at baseline to
1.3±0.2 and 1.6±0.1
mL · min-1 · dL-1 after 15 and 40
minutes, respectively, arguing against a progressive vasoconstrictor
effect after 15 minutes of infusion.
Effects of NO Synthase Blockade on Vasodilator
Responses
Fig 1
illustrates the FBF response to the six
increasing adenosine dosages during the placebo and L-NMMA
infusions. Adenosine in the presence of placebo induced a
dose-dependent increase in FBF from 2.3±0.2 to 15.9±3.1
mL · min-1 · dL-1. During coinfusion
with L-NMMA, adenosine increased FBF from 1.7 to 10.0
mL · min-1 · dL-1, this
response being significantly reduced compared with the first
dose-response curve. The concomitant infusion of L-NMMA and
adenosine elicited no significant changes in contralateral FBF
(from 1.8±0.2
mL · min-1 · dL-1 at
baseline to 2.3±0.3
mL · min-1 · dL-1 at the highest
adenosine dose), mean arterial pressure (from 80±4
to 83±4 mm Hg), or heart rate (from 55±2 to 54±2 beats per
minute).
|
In the second series of experiments, the vasoconstrictor effect of
L-NMMA was counteracted by concomitant infusion of SNP. Again, in the
presence of placebo, adenosine caused a dose-dependent
forearm vasodilator effect with an increase of FBF from 1.9±0.4 to
14.9±2.0 mL · min-1 · dL-1 (Fig 2
). After conditions returned to baseline, the combined
infusion of L-NMMA and SNP did not significantly change FBF (2.0±0.3
versus 2.2±0.3 mL · min-1 · dL-1;
n=6, P=NS). The subsequent administration of the six
adenosine dosages elicited dose-dependent increments in FBF
from 2.2±0.3 to 9.8±2.4
mL · min-1 · dL-1; the changes
from baseline were significantly reduced compared with those before
administration of L-NMMA and SNP (P<.01) (Fig 2
). No
significant changes occurred in contralateral FBF (from 1.7±0.3
mL · min-1 · dL-1 at baseline to
1.8±0.3 mL · min-1 · dL-1 at the
highest adenosine dose), mean arterial pressure
(from 79±4 to 81±3 mm Hg), or heart rate (from 53±2 to 53±3 beats
per minute).
|
The intra-arterial infusion of L-NMMA did not change the forearm vasodilator response to verapamil. During placebo, the FBF changes from baseline for the four increasing verapamil dosages averaged 2.3±0.5, 4.2±0.7, 8.6±1.9, and 11.9±2.8 mL · min-1 · dL-1, whereas these numbers were 1.7±0.2, 3.5±0.9, 6.7±1.4, and 12.2±2.4 mL · min-1 · dL-1 during concomitant L-NMMA administration. No significant effects on systemic hemodynamics were observed during the combined infusion of L-NMMA and verapamil. The contralateral FBF was 1.9±0.2 mL · min-1 · dL-1 before and 1.6±0.3 mL · min-1 · dL-1 during the highest verapamil dose. Respective values for mean arterial blood pressure were 79±2 and 79±2 mm Hg, and for heart rate they were 56±4 and 58±4 beats per minute.
Effects of Potassium Channel Blockade on Adenosine
Responses
Fig 3
demonstrates the effects of tolbutamide on
the vasodilator response to adenosine. Tolbutamide infusion
into the brachial artery did not change the baseline FBF (2.3±0.3
versus 2.2±0.3 mL · min-1 · dL-1).
Moreover, the adenosine-induced increase in FBF was not
reduced by tolbutamide.
|
Fig 4
illustrates the effects of quinidine on the
forearm vasodilator response to adenosine infusion. In this
series, adenosine increased FBF from 1.6±0.3 to 9.0±0.8
mL · min-1 · dL-1. After
equilibration, the FBF returned to a baseline value of 1.5
mL · min-1 · dL-1. Ten minutes of
quinidine infusion increased the baseline FBF significantly to 2.9±0.7
mL · min-1 · dL-1
(P<.05). However, regional quinidine infusion did not
significantly affect the adenosine-induced increase in FBF
from baseline.
|
Throughout these two series of experiments, there were no changes in contralateral FBF, blood pressure, or heart rate. The plasma insulin concentrations averaged 4.4±1.2 µU/mL before and 4.5±1.2 µU/mL after tolbutamide administration (P=NS), and the glucose levels were 84±3 and 81±2 mg/dL, respectively (P=NS).
| Discussion |
|---|
|
|
|---|
Several recent studies in animals support our observations,4 5 8 34 but others do not.2 35 Species differences and different experimental conditions may contribute to this discrepancy. In the perfused-forearm technique used in this study, the drug is administered into the vascular lumen, so the exposure to adenosine is much higher for the vascular endothelium than for the underlying smooth muscle cell layer, especially because of the efficient uptake of adenosine by the endothelium.36 37 In several in vitro vascular preparations, the exposure is more balanced, and therefore direct relaxant effects on smooth muscle cells mediated by stimulation of A2-adenosine receptors may have been more pronounced.37
Shear Stress as a Mechanism of Action
A number of transducing mechanisms should be considered as
mediators for the ability of adenosine to release
endothelium-derived NO. For example, the
adenosine-induced release of NO might have been triggered
nonspecifically by the increase in flow (shear stress) rather than by
the specific stimulation of endothelial
adenosine receptors. However, in previous studies in which the
same technique was used, the intra-arterial infusion of
L-NMMA reduced the relaxant effects of acetylcholine but not those of
SNP, arguing against a contribution of flow-related NO release
during drug-induced elevations of FBF.38 Furthermore,
in the present study, L-NMMA did not attenuate the vasodilator
response to the calcium entry blocker verapamil, an
endothelium-independent vasodilator, despite
production of blood flow responses comparable to those observed
in the middle of the dosage range of adenosine. Our data
therefore point toward a more specific interaction between L-NMMA and
adenosine. We and others previously showed that low
intrabrachial dosages of the adenosine receptor
antagonists caffeine and theophylline are able to block the
forearm vasodilator response to adenosine,21 39
enabling us to postulate that the adenosine-mediated
release of NO results from stimulation of endothelial
adenosine receptors. Unfortunately, selective agonists and
antagonists for the different subtypes of adenosine
receptors are not available for human use, so it is not possible at
this time to determine whether the adenosine-induced NO
release in humans is mediated by stimulation of
endothelial A1- or
A2-adenosine receptors.
Role of Potassium Channels
We postulated that activation of potassium channels may serve as
an intermediate step, transducing stimulation of adenosine
receptors to the synthesis and/or release of NO from the
endothelium. Because equipotent dosages of the related
sulfonylurea derivative glibenclamide have been shown to attenuate the
vasodilator response to pharmacological opening of KATP
channels in the forearm vascular bed,40 41 we think that
our negative observation of tolbutamide cannot be attributed to
ineffective dosing. Consequently, our data support the conclusion that
opening of the KATP channel does not contribute to the
vasodilator response to intra-arterial
adenosine infusion in humans. In theory, KATP
channel opening might have contributed to the vasoactive effects of
adenosine at two different levels. At the level of the
endothelium, KATP channel opening may
hyperpolarize endothelial cells, and may thereby
activate endothelial NO release by increasing
the influx of calcium.42 In contrast to increases of
calcium influx in endothelial cells after
hyperpolarization, calcium influx decreases after
membrane hyperpolarization in vascular smooth
muscle cells.42 Therefore, opening of potassium channels
also results in vasodilation at the level of vascular smooth muscle
cells. It must be emphasized that because of our intraluminal
administration of adenosine, its effects may have been
predominantly endothelium dependent, and therefore we
think that our tolbutamide data do not exclude a role of
KATP channel activation in the smooth musclerelaxing
effects of adenosine.
Although we realize that quinidine has several pharmacological
properties, including sodium channel blockade and
antiadrenergic effects, its recently established
potassium channelblocking properties made this drug an additional
tool for our study, especially because quinidine was able to attenuate
the vasodilator response to adenosine in animal
studies.43 Quinidine increased basal FBF but did not
attenuate the vasodilator response to adenosine. The effect of
quinidine on the baseline flow may well be explained by its
-adrenergicblocking properties. In line with the reasoning
on tolbutamide, our data argue against a role of
quinidine-sensitive potassium channels in the
adenosine-mediated release of NO but do not exclude an
interaction between quinidine and adenosine at the level of
vascular smooth muscle cells.
Pathophysiological
Implications
Apart from effects on vascular tone, adenosine has other
important properties, including inhibition of platelet
aggregation,44 inhibition of leukocyte
activation,45 and presynaptic inhibition of
noradrenaline release.46 Furthermore,
adenosine appears to mediate ischemic preconditioning
in the myocardium.47 The release of
endogenous adenosine may also contribute to the
reactive hyperemic response after
ischemia14 48 as well as to exercise-induced
vasodilation.49 In recent years, NO has been demonstrated
to affect several of these pathophysiological
phenomena in a similar way.14 48 50 51 52 53 Because
adenosine is released from tissues, including the
endothelium, during anoxia or
ischemia,54 the currently observed relation
between adenosine and endothelial NO release
makes endogenous adenosine a likely candidate for
triggering NO release during ischemia. We believe that our
results create the foundation for future studies on the interrelation
between the release of endogenous adenosine and
that of NO in several pathophysiological
conditions in humans.
| Selected Abbreviations and Acronyms |
|---|
|
| Acknowledgments |
|---|
Received January 26, 1995; revision received April 26, 1995; accepted May 3, 1995.
| References |
|---|
|
|
|---|
2. White DG, Drew GM, Gurden JM, Penny DM, Roach AG, Watts IS. The effect of NG-nitro-L-arginine methyl ester upon basal blood flow and endothelium-dependent vasodilation in the dog hindlimb. Br J Pharmacol. 1993;108:763-768. [Medline] [Order article via Infotrieve]
3.
Treasure CB, Vita JA, Cox DA, Fish D, Gordon JB, Mudge
GH, Colucci WS, St John Sutton MG, Selwijn AP, Alexander RW, Ganz P.
Endothelium-dependent dilation of the
coronary microvasculature is impaired in dilated
cardiomyopathy.
Circulation. 1990;81:772-779.
4. Vials A, Burnstock G. A2-purinoceptor-mediated relaxation in the guinea-pig coronary vasculature: a role for nitric oxide. Br J Pharmacol. 1993;109:424-429. [Medline] [Order article via Infotrieve]
5.
Okamura M, Miura K, Yamashita Y, Yukimura T, Yamamoto
K. Role of endothelium-derived relaxing
factor in the in vivo renal vascular action of adenosine in
dogs. J Exp Pharmacol Ther. 1992;260:1262-1267.
6.
Headrick JP, Berne RM.
Endothelium-dependent and -independent
relaxations to adenosine in guinea pig aorta. Am
J Physiol. 1990;259:H62-H67.
7. Iwamoto T, Umemura S, Toya Y, et al. Identification of adenosine A2 receptor-cAMP system in human aortic endothelial cells. Biochem Biophys Res Commun. 1994;199:905-910. [Medline] [Order article via Infotrieve]
8. Rose'Meyer RB, Hope W. Evidence that A2-purinoceptors are involved in endothelium-dependent relaxation of the rat thoracic aorta. Br J Pharmacol. 1990;100:576-580. [Medline] [Order article via Infotrieve]
9. Balcells E, Suarez J, Rubio R. Functional role of intravascular coronary endothelial adenosine receptors. Eur J Pharmacol. 1992;210:1-9. [Medline] [Order article via Infotrieve]
10. Moncada S. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev. 1991;43:109-142. [Medline] [Order article via Infotrieve]
11.
Kirsch GE, Codina J, Birnbaumer L, Brown AM.
Coupling of ATP-sensitive K-channels to A1-receptors by G
proteins in rat ventricular myocytes. Am J
Physiol. 1990;259:H820-H826.
12.
Liao JK, Homcy CJ. The G proteins of the
G
i and G
q family couple the bradykinin
receptor to the release of endothelium-derived
relaxing factor. J Clin Invest. 1993;92:2168-2172.
13. Seiss-Geuder M, Mehrke G, Daut J. Sustained hyperpolarization of cultured guinea pig coronary endothelial cells induced by adenosine. J Cardiovasc Pharmacol. 1992;20(suppl 12):S97-S100.
14.
Leipert B, Becker BF, Gerlach E. Different
endothelial mechanisms involved in coronary
responses to known vasodilators. Am J Physiol. 1992;262:H1676-H1683.
15. Cooke JP, Rossitch E, Andon NA, Loscalzo J, Dzau VJ. Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator. J Clin Invest. 1991;88:1663-1671.
16. Lüscher TF, Vanhoutte PM. Endothelium-dependent responses in human blood vessels: human versus animals. Trends Pharmacol Sci. 1988;9:181-184. [Medline] [Order article via Infotrieve]
17.
Kiowski W, Linder L, Stoschitzky K, et al.
Diminished vascular response to inhibition of
endothelium-derived nitric oxide and enhanced
vasoconstriction to exogenously administered endothelin-1 in clinically
healthy smokers. Circulation. 1994;90:27-34.
18. Panza JA, Quyyumi AA, Brush JE, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323:22-27. [Abstract]
19. Creager MA, Gallagher SJ, Girerd XJ, Coleman SM, Dzau VJ, Cooke JP. L-Arginine improves endothelium-dependent vasodilation in hypercholesterolemic patients. J Clin Invest. 1992;90:1248-1253.
20.
Gilligan DM, Guetta V, Panza JA, Garcia CE, Quyyumi AA,
Cannon RO III. Selective loss of microvascular
endothelial function in human
hypercholesterolemia.
Circulation. 1994;90:35-41.
21. Smits P, Lenders JWM, Thien T. Caffeine and theophylline attenuate adenosine-induced vasodilation in humans. Clin Pharmacol Ther. 1990;48:410-418. [Medline] [Order article via Infotrieve]
22. Lenders J, Janssen G-J, Smits P, Thien T. Role of the wrist cuff in forearm plethysmography. Clin Sci. 1991;80:413-417. [Medline] [Order article via Infotrieve]
23. Vallance PCJ, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet. 1989;2:997-1000. [Medline] [Order article via Infotrieve]
24. Myers HA, Honig CR. Influence of initial resistance on magnitude of response to vasomotor stimuli. Am J Physiol. 1969;216:1429-1436.
25.
Koller A, Sun D, Huang A, Kaley G. Corelease of
nitric oxide and prostaglandins mediates flow-dependent
dilation of rat gracilis muscle arterioles. Am J
Physiol. 1994;267:H326-H332.
26. Meisheri KD, Khan SA, Martin JL. Vascular pharmacology of ATP-sensitive K-channels: interactions between glyburide and K-channel-openers. J Vasc Res. 1993;30:2-12. [Medline] [Order article via Infotrieve]
27.
Anderson EA, Mark AL. The vasodilator action of
insulin: implications for the insulin hypothesis of
hypertension. Hypertension. 1993;21:136-141.
28.
Lembo G, Rendina V, Iaccarino G, Lamenza F, Volpe M,
Trimarco B. Insulin reduces reflex forearm sympathetic
vasoconstriction in healthy humans.
Hypertension. 1993;21:1015-1019.
29. Benz I, Kohlhardt M. Blockade of cardiac outwardly rectifying K-channels by TEA and class III antiarrhythmics: evidence against a single drug-sensitive channel site. Eur Biophys J. 1994;22:437-446. [Medline] [Order article via Infotrieve]
30.
Imaizumi Y, Giles WR. Quinidine-induced
inhibition of transient outward current in cardiac muscle.
Am J Physiol. 1987;253:H704-H708.
31.
Richards NW, Dawson DC. Single potassium
channels blocked by lidocaine and quinidine in isolated turtle colon
epithelial cells. Am J Physiol. 1986;251:C85-C89.
32.
Salata JJ, Wasserstrom JA. Effects of quinidine
on action potentials and ionic currents in isolated canine
ventricular myocytes. Circ
Res. 1988;62:324-337.
33.
Roden DM, Bennett PB, Snyders DJ, Balser JR, Hondeghem
LM. Quinidine delays Ik-activation in guinea pig
ventricular myocytes. Circ
Res. 1988;62:1055-1058.
34. Read MA, Boura ARA, Walters WAW. Vascular action of purines in the foetal circulation of the human placenta. Br J Pharmacol. 1993;110:454-460. [Medline] [Order article via Infotrieve]
35.
Kirkeboen KA, Naess PA, Offstad J, Ilebekk A.
Effects of regional inhibition of nitric oxide synthesis in
intact porcine hearts. Am J Physiol. 1994;266:H1516-H1527.
36. Nees S, Herzog V, Becker BF, Bock M, Des Rosier CEG. The coronary endothelium: a highly active metabolic barrier for adenosine. Basic Res Cardiol. 1985;80:515-529. [Medline] [Order article via Infotrieve]
37.
Headrick JP, Northington FJ, Hynes MR, Matherne GP,
Berne RM. Relative responses to luminal and adventitial
adenosine in perfused arteries. Am J
Physiol. 1992;263:H1437-H1446.
38.
Rongen G, Smits P, Thien TH. Characterization of
ATP-induced vasodilation in the human forearm vascular bed.
Circulation. 1994;90:1891-1898.
39. Taddei S, Pedrinelli R, Salvetti A. Theophylline is an antagonist of adenosine in human forearm arterioles. Am J Hypertens. 1991;4:256-259. [Medline] [Order article via Infotrieve]
40. Ashcroft SJH, Ashcroft FM. Properties and functions of ATP-sensitive potassium channels. Cell Signal. 1990;2:197-214. [Medline] [Order article via Infotrieve]
41. Bijlstra PJ, Smits P, Lutterman JA, Thien TH. Glibenclamide inhibits the vasodilator effect of potassium channel activation in man. Diabetologia. 1994;37(suppl 1):A162. Abstract.
42.
Janigro D, West GA, Gorden EL, Winn HR.
ATP-sensitive K+-channels in rat aorta and brain
microvascular endothelial cells. Am J
Physiol. 1993;265:C812-C821.
43.
Burnstock G. Purinergic nerves.
Pharmacol Rev. 1972;24:509-581.
44. Edlund A, Siden Å, Sollevi A. Evidence for an anti-aggregatory effect of adenosine at physiological concentrations and for its role in the action of dipyridamole. Thromb Res. 1987;45:183-190. [Medline] [Order article via Infotrieve]
45. Cronstein BC, Levin RI, Belanoff J, Weissmann G, Hirschhorn R. Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells. J Clin Invest. 1986;78:760-770.
46. Wennmalm M, Fredholm BB, Hedqvist P. Adenosine as a modulator of sympathetic nerve-stimulation-induced release of noradrenaline from the isolated rabbit heart. Acta Physiol Scand. 1988;132:487-494. [Medline] [Order article via Infotrieve]
47.
Toombs CF, McGee DS, Johnston WE, Vinten-Johansen J.
Myocardial protective effects of adenosine: infarct size
reduction with pretreatment and continued receptor stimulation during
ischemia. Circulation. 1992;86:986-994.
48.
Maekawa K, Saito D, Obayashi N, Uchida S, Haraoka S.
Role of endothelium-derived nitric oxide and
adenosine in functional myocardial hyperemia.
Am J Physiol. 1994;267:H166-H173.
49.
Goonewardene IP, Karim F. Attenuation of
exercise-induced vasodilation by adenosine deaminase in
anaesthetized dogs. J Physiol. 1991;442:65-79.
50. Clancy RM, Leszczynska-Piziak J, Abramson SB. Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase. J Clin Invest. 1992;90:1116-1121.
51.
Siegfried MR, Erhardt J, Rider T, Ma XL, Lefer AM.
Cardioprotection and attenuation of endothelial
dysfunction by organic nitric oxide donors in myocardial
ischemia-reperfusion. J Pharmacol
Exp Ther. 1992;260:668-675.
52. Vegh A, Szekeres L, Parratt J. Preconditioning of the ischaemic myocardium: involvement of the L-arginine nitric oxide pathway. Br J Pharmacol. 1992;107:648-652. [Medline] [Order article via Infotrieve]
53.
Loscalzo J, Vita JA. Ischemia,
hyperemia, exercise, and nitric oxide: complex physiology and
complex molecular adaptations.
Circulation. 1994;90:2556-2559.
54.
Smolenski RT, Kochan Z, McDouall R, Page C, Seymour
A-ML, Yacoub MH. Endothelial
nucleotide catabolism and adenosine
production. Cardiovasc Res. 1994;28:100-104.
This article has been cited by other articles:
![]() |
J. L. Vega, C. Puebla, R. Vasquez, M. Farias, J. Alarcon, M. Pastor-Anglada, B. Krause, P. Casanello, and L. Sobrevia TGF-{beta}1 inhibits expression and activity of hENT1 in a nitric oxide-dependent manner in human umbilical vein endothelium Cardiovasc Res, June 1, 2009; 82(3): 458 - 467. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. P. Mortensen, M. Nyberg, P. Thaning, B. Saltin, and Y. Hellsten Adenosine Contributes to Blood Flow Regulation in the Exercising Human Leg by Increasing Prostaglandin and Nitric Oxide Formation Hypertension, June 1, 2009; 53(6): 993 - 999. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. P. Mortensen, J. Gonzalez-Alonso, L. T. Bune, B. Saltin, H. Pilegaard, and Y. Hellsten ATP-induced vasodilation and purinergic receptors in the human leg: roles of nitric oxide, prostaglandins, and adenosine Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2009; 296(4): R1140 - R1148. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. J. Ray and J. M. Marshall Nitric oxide (NO) does not contribute to the generation or action of adenosine during exercise hyperaemia in rat hindlimb J. Physiol., April 1, 2009; 587(7): 1579 - 1591. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Shibasaki, D. A. Low, S. L. Davis, and C. G. Crandall Nitric oxide inhibits cutaneous vasoconstriction to exogenous norepinephrine J Appl Physiol, November 1, 2008; 105(5): 1504 - 1508. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. J. Van der Schueren, A. Rogiers, F. H. Vanmolkot, A. Van Hecken, M. Depre, S. A. Kane, I. De Lepeleire, S. R. Sinclair, and J. N. de Hoon Calcitonin Gene-Related Peptide8-37 Antagonizes Capsaicin-Induced Vasodilation in the Skin: Evaluation of a Human in Vivo Pharmacodynamic Model J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 248 - 255. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Marshall The roles of adenosine and related substances in exercise hyperaemia J. Physiol., September 15, 2007; 583(3): 835 - 845. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Raher, H. Thibault, K. K. Poh, R. Liu, E. F. Halpern, G. Derumeaux, F. Ichinose, W. M. Zapol, K. D. Bloch, M. H. Picard, et al. In Vivo Characterization of Murine Myocardial Perfusion With Myocardial Contrast Echocardiography: Validation and Application in Nitric Oxide Synthase 3 Deficient Mice Circulation, September 11, 2007; 116(11): 1250 - 1257. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Merla, Y. Ye, Y. Lin, S. Manickavasagam, M.-H. Huang, R. J. Perez-Polo, B. F. Uretsky, and Y. Birnbaum The central role of adenosine in statin-induced ERK1/2, Akt, and eNOS phosphorylation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1918 - H1928. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Ye, Y. Lin, R. Perez-Polo, M.-H. Huang, M. G. Hughes, D. J. McAdoo, S. Manickavasagam, B. F. Uretsky, and Y. Birnbaum Enhanced cardioprotection against ischemia-reperfusion injury with a dipyridamole and low-dose atorvastatin combination Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H813 - H818. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Hirata, A. Kadirvelu, M. Di Tullio, S. Homma, A. M. Choy, and C. C. Lang Coronary Vasomotor Function Is Abnormal in First-Degree Relatives of Patients With Type 2 Diabetes Diabetes Care, January 1, 2007; 30(1): 150 - 153. [Full Text] [PDF] |
||||
![]() |
K. K. Kalliokoski, H. Langberg, A. K. Ryberg, C. Scheede-Bergdahl, S. Doessing, A. Kjaer, M. Kjaer, and R. Boushel Nitric oxide and prostaglandins influence local skeletal muscle blood flow during exercise in humans: coupling between local substrate uptake and blood flow Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R803 - R809. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. A. Martin, W. T. Nicholson, J. H. Eisenach, N. Charkoudian, and M. J. Joyner Bimodal distribution of vasodilator responsiveness to adenosine due to difference in nitric oxide contribution: implications for exercise hyperemia J Appl Physiol, August 1, 2006; 101(2): 492 - 499. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. L. E. Vicario, L. Cirillo, G. Storto, T. Pellegrino, N. Ragone, L. Fontanella, M. Petretta, D. Bonaduce, and A. Cuocolo Influence of Risk Factors on Coronary Flow Reserve in Patients with 1-Vessel Coronary Artery Disease J. Nucl. Med., September 1, 2005; 46(9): 1438 - 1443. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. O. Prior, M. J. Quinones, M. Hernandez-Pampaloni, A. D. Facta, T. H. Schindler, J. W. Sayre, W. A. Hsueh, and H. R. Schelbert Coronary Circulatory Dysfunction in Insulin Resistance, Impaired Glucose Tolerance, and Type 2 Diabetes Mellitus Circulation, May 10, 2005; 111(18): 2291 - 2298. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. A. Kaufmann and P. G. Camici Myocardial Blood Flow Measurement by PET: Technical Aspects and Clinical Applications J. Nucl. Med., January 1, 2005; 46(1): 75 - 88. [Full Text] [PDF] |
||||
![]() |
N. P. Riksen, G. A. Rongen, G. H.J. Boers, H. J. Blom, P. H.H. van den Broek, and P. Smits Enhanced Cellular Adenosine Uptake Limits Adenosine Receptor Stimulation in Patients With Hyperhomocysteinemia Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 109 - 114. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. A. Kaufmann, O. Rimoldi, T. Gnecchi-Ruscone, R. S. Bonser, T. F. Luscher, and P. G. Camici Systemic Inhibition of Nitric Oxide Synthase Unmasks Neural Constraint of Maximal Myocardial Blood Flow in Humans Circulation, September 14, 2004; 110(11): 1431 - 1436. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. B. Rosenmeier, S. J. Fritzlar, F. A. Dinenno, and M. J. Joyner Exogenous NO administration and {alpha}-adrenergic vasoconstriction in human limbs J Appl Physiol, December 1, 2003; 95(6): 2370 - 2374. [Abstract] [Full Text] |
||||
![]() |
A. Gamboa, A. C. Ertl, F. Costa, G. Farley, M. L. Manier, D. L. Hachey, A. Diedrich, and I. Biaggioni Blockade of Nucleoside Transport Is Required for Delivery of Intraarterial Adenosine Into the Interstitium: Relevance to Therapeutic Preconditioning in Humans Circulation, November 25, 2003; 108(21): 2631 - 2635. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. F. Di Carli, J. Janisse, G. Grunberger, and J. Ager Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes J. Am. Coll. Cardiol., April 16, 2003; 41(8): 1387 - 1393. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Kjaer, C. Meyer, F. S. Nielsen, H.-H. Parving, and B. Hesse Dipyridamole, Cold Pressor Test, and Demonstration of Endothelial Dysfunction: A PET Study of Myocardial Perfusion in Diabetes J. Nucl. Med., January 1, 2003; 44(1): 19 - 23. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Gregorini, J. Marco, B. Farah, M. Bernies, C. Palombo, M. Kozakova, I. M. Bossi, B. Cassagneau, J. Fajadet, C. Di Mario, et al. Effects of Selective {alpha}1- and {alpha}2-Adrenergic Blockade on Coronary Flow Reserve After Coronary Stenting Circulation, December 3, 2002; 106(23): 2901 - 2907. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Paiva, J. Laakso, H. Laine, R. Laaksonen, J. Knuuti, and O. T. Raitakari Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1241 - 1247. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. W. WYATT, J. R. STEINERT, C. P. D. WHEELER-JONES, A. J. MORGAN, D. SUGDEN, J. D. PEARSON, L. SOBREVIA, and G. E. MANN Early activation of the p42/p44MAPK pathway mediates adenosine-induced nitric oxide production in human endothelial cells: a novel calcium-insensitive mechanism FASEB J, October 1, 2002; 16(12): 1584 - 1594. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Tawakol, M. A. Forgione, M. Stuehlinger, N. M. Alpert, J. P. Cooke, J. Loscalzo, A. J. Fischman, M. A. Creager, and H. Gewirtz Homocysteine impairs coronary microvascular dilator function in humans J. Am. Coll. Cardiol., September 18, 2002; 40(6): 1051 - 1058. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Boushel, H. Langberg, C. Gemmer, J. Olesen, R. Crameri, C. Scheede, M. Sander, and M. Kjaer Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise J. Physiol., September 1, 2002; 543(2): 691 - 698. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. O. Bonetti, S. H. Wilson, M. Rodriguez-Porcel, D. R. Holmes Jr, L. O. Lerman, and A. Lerman Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering J. Am. Coll. Cardiol., August 7, 2002; 40(3): 546 - 554. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. B. Gordon, R. Jain, J. A Beckman, and M. A Creager The contribution of nitric oxide to exercise hyperemia in the human forearm Vascular Medicine, August 1, 2002; 7(3): 163 - 168. [Abstract] [PDF] |
||||
![]() |
I. Feoktistov, A. E. Goldstein, S. Ryzhov, D. Zeng, L. Belardinelli, T. Voyno-Yasenetskaya, and I. Biaggioni Differential Expression of Adenosine Receptors in Human Endothelial Cells: Role of A2B Receptors in Angiogenic Factor Regulation Circ. Res., March 22, 2002; 90(5): 531 - 538. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Nakamura, K. Egashira, K. Arimura, Y. Machida, T. Ide, H. Tsutsui, H. Shimokawa, and A. Takeshita Increased inactivation of nitric oxide is involved in impaired coronary flow reserve in heart failure Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2619 - H2625. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. H. Buus, M. Bottcher, F. Hermansen, M. Sander, T. T. Nielsen, and M. J. Mulvany Influence of Nitric Oxide Synthase and Adrenergic Inhibition on Adenosine-Induced Myocardial Hyperemia Circulation, November 6, 2001; 104(19): 2305 - 2310. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. K. Naber, D. Baumgart, C. Altmann, W. Siffert, R. Erbel, and G. Heusch eNOS 894T allele and coronary blood flow at rest and during adenosine-induced hyperemia Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1908 - H1912. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Grossmann, D. Dobrev, H. M. Himmel, U. Ravens, and W. Kirch Ascorbic Acid-Induced Modulation of Venous Tone in Humans Hypertension, March 1, 2001; 37(3): 949 - 954. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. A. Kaufmann, T. Gnecchi-Ruscone, M. di Terlizzi, K. P. Schafers, T. F. Luscher, and P. G. Camici Coronary Heart Disease in Smokers : Vitamin C Restores Coronary Microcirculatory Function Circulation, September 12, 2000; 102(11): 1233 - 1238. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. A. Kaufmann, T. Gnecchi-Ruscone, K. P. Schafers, T. F. Luscher, and P. G. Camici Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia J. Am. Coll. Cardiol., July 1, 2000; 36(1): 103 - 109. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Tang, M. Parker, Q. Fei, and R. Loutzenhiser Afferent arteriolar adenosine A2a receptors are coupled to KATP in in vitro perfused hydronephrotic rat kidney Am J Physiol Renal Physiol, December 1, 1999; 277(6): F926 - F933. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Duffy, S. F. Castle, R. W. Harper, and I. T. Meredith Contribution of Vasodilator Prostanoids and Nitric Oxide to Resting Flow, Metabolic Vasodilation, and Flow-Mediated Dilation in Human Coronary Circulation Circulation, November 9, 1999; 100(19): 1951 - 1957. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. F. Di Carli, D. Bianco-Batlles, M. E. Landa, A. Kazmers, H. Groehn, O. Muzik, and G. Grunberger Effects of Autonomic Neuropathy on Coronary Blood Flow in Patients With Diabetes Mellitus Circulation, August 24, 1999; 100(8): 813 - 819. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. B. Anning, B. D. Prendergast, P. A. MacCarthy, A. M. Shah, D. C. Buss, and M. J. Lewis ATP is involved in myocardial and vascular effects of exogenous bradykinin in ejecting guinea pig heart Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H818 - H825. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Baller, G. Notohamiprodjo, U. Gleichmann, J. Holzinger, R. Weise, and J. Lehmann Improvement in Coronary Flow Reserve Determined by Positron Emission Tomography After 6 Months of Cholesterol-Lowering Therapy in Patients With Early Stages of Coronary Atherosclerosis Circulation, June 8, 1999; 99(22): 2871 - 2875. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Costa, P. Sulur, M. Angel, J. Cavalcante, V. Haile, B. Christman, and I. Biaggioni Intravascular Source of Adenosine During Forearm Ischemia in Humans : Implications for Reactive Hyperemia Hypertension, June 1, 1999; 33(6): 1453 - 1457. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. S. Huggins, R. C. Pasternak, N. M. Alpert, A. J. Fischman, and H. Gewirtz Effects of Short-Term Treatment of Hyperlipidemia on Coronary Vasodilator Function and Myocardial Perfusion in Regions Having Substantial Impairment of Baseline Dilator Reverse Circulation, September 29, 1998; 98(13): 1291 - 1296. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. W. Daniels, P. A. Mole, J. D. Shaffrath, and C. L. Stebbins Effects of caffeine on blood pressure, heart rate, and forearm blood flow during dynamic leg exercise J Appl Physiol, July 1, 1998; 85(1): 154 - 159. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Costa and I. Biaggioni Role of Nitric Oxide in Adenosine-Induced Vasodilation in Humans Hypertension, May 1, 1998; 31(5): 1061 - 1064. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Cardillo, C. M. Kilcoyne, A. A. Quyyumi, R. O. Cannon III, and J. A. Panza Selective Defect in Nitric Oxide Synthesis May Explain the Impaired Endothelium-Dependent Vasodilation in Patients With Essential Hypertension Circulation, March 10, 1998; 97(9): 851 - 856. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. A. Recchia, H. Senzaki, A. Saeki, B. J. Byrne, and D. A. Kass Pulse Pressure–Related Changes in Coronary Flow In Vivo Are Modulated by Nitric Oxide and Adenosine Circ. Res., October 1, 1996; 79(4): 849 - 856. [Abstract] [Full Text] |
||||
![]() |
I. Feoktistov, A. E. Goldstein, S. Ryzhov, D. Zeng, L. Belardinelli, T. Voyno-Yasenetskaya, and I. Biaggioni Differential Expression of Adenosine Receptors in Human Endothelial Cells: Role of A2B Receptors in Angiogenic Factor Regulation Circ. Res., March 22, 2002; 90(5): 531 - 538. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 1995 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |