(Circulation. 2000;101:1848.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Stimulation of Bradykinin B1 Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs
Comparison With B2 Receptor Stimulation
From INSERM U400, Faculté de Médecine, Créteil, France, and the Département de Pharmacologie (F.B., A.B.), Hôpital Kremlin-Bicêtre, Kremlin Bicêtre, France.
Correspondence to Luc Hittinger, MD, INSERM U400, Hôpital Léon Bernard, 94456 Limeil Brévannes, France. E-mail hittinger{at}im3.inserm.fr
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Abstract |
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Background—Constitutive bradykinin B1 receptors have been identified in dogs; however, their physiological implications involving the coronary circulation remain to be determined. This study examined, in conscious dogs, the coronary response to des-Arg9-bradykinin (a B1 receptor agonist) and the mechanisms involved.
Methods and Results—Eleven dogs were instrumented with a left
ventricular micromanometer, a
circumflex coronary catheter, a cuff occluder, a Doppler
flow probe, and ultrasonic crystals to measure coronary blood
flow velocity (CBFv) and coronary diameter (CD).
Intracoronary des-Arg9-bradykinin (3 to 100 ng/kg)
and bradykinin (0.1 to 10 ng/kg) did not modify systemic
hemodynamics but dose-dependently increased CBFv and
CD. Des-Arg9-bradykinin was less potent than bradykinin.
Hoe 140 (a B2 antagonist, 10 µg/kg) abolished
the effects of bradykinin but did not influence the effects of
des-Arg9-bradykinin. When CBFv increase was prevented by
the cuff occluder, CD responses to bradykinin and
des-Arg9-bradykinin were maintained. Intracoronary
lisinopril (0.75 mg) increased the CD response to
bradykinin, with only minimal effect on CBFv, and extended the duration
of the effect. Lisinopril did not alter
des-Arg9-bradykinin responses. Intracoronary
N
-nitro-L-arginine (2 mg/kg)
decreased the CD effect of bradykinin and prevented the CBFv and CD
effects of des-Arg9-bradykinin. The relaxing effect of
des-Arg9-bradykinin on isolated coronary rings was
prevented by
des-Arg9,[Leu8]-bradykinin.
Conclusions—In the conscious dog, B1 receptors are present in coronary vessels, and their stimulation produces vasodilation in conductance and resistance vessels, which is mediated essentially by NO but not modulated by angiotensin-converting enzyme. However, the coronary vasodilation induced by B1 receptor stimulation is not as great as that produced by B2 receptor stimulation.
Key Words: bradykinin • nitric oxide • receptors • vasodilation
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Introduction |
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Kinin receptors are classified as B1 and B2 receptors, according to their sensitivity to different agonists and antagonists.1 The existence of B1 and B2 receptors has been confirmed by cloning and pharmacological characterizations in humans.2 3 Kinins exert their vascular effects through B2 and B1 receptors. B2 receptors are constitutively present in most tissues of various species. B2 receptors are sensitive to bradykinin and kallidin (Lys-bradykinin), whereas B1 receptors are relatively insensitive to these compounds but sensitive to des-Arg9-bradykinin and Lys-des-Arg9-bradykinin, natural metabolites of bradykinin and Lys-bradykinin induced by kininase I (carboxypeptidase N).1 The activation of B2 receptors can elicit complex responses reflecting the multiple actions of agonists in endothelial cells, vascular smooth muscle, and nerve endings. B1 receptors, absent in normal vessels from some animal species, are inducible and functionally expressed in response to cytokines, bacterial lipopolysaccharides, and in vitro tissue incubation.4 5 6 However, B1 receptors are heterogeneously expressed depending on species and tissues.7 B1 receptors are constitutively and functionally expressed in the arterial vessels and glomerulus of rats,8 9 in the pulmonary vascular bed of cats,10 and in the arterial vessels of pigs11 and dogs.12 13 14 In humans, a recent in vitro study using immunolabeling techniques revealed the presence of B1 receptors in vascular endothelial and smooth muscle cells of large elastic arteries, muscular arteries (such as coronary arteries), and muscular arterioles.15 The functional role of constitutive B1 receptors in the arterial vessels of dogs is well documented.12 13 14 The stimulation of these receptors produces a vasorelaxation and a reduction in blood pressure.12 13 14 However, their physiological implications in the coronary circulation remain to be determined. Therefore, the present study was designed to examine, in conscious dogs, the coronary effects of B1 receptor stimulation and the mechanisms involved. This was accomplished by injecting des-Arg9-bradykinin into the circumflex coronary artery through a chronically implanted catheter at doses that did not induce systemic changes. To determine the potency of B1 receptor stimulation, the effects of des-Arg9-bradykinin were compared with those of bradykinin. To distinguish the direct versus the flow-mediated effects of des-Arg9-bradykinin and bradykinin on large coronary vessels, the effects of des-Arg9-bradykinin and bradykinin on coronary diameter (CD) were examined when coronary blood flow (CBF) increase was prevented by inflation of a cuff occluder. In addition, because angiotensin-converting enzyme (ACE) inhibition can potentiate the vasodilator effects of bradykinin, a series of experiments was performed to determine the influence of an ACE inhibitor, lisinopril, on the effects of intracoronary des-Arg9-bradykinin and bradykinin. Finally, to assess the role of NO in the effects of B1 receptor stimulation, a series of experiments was performed after the administration of N
-nitro-L-arginine
(LNA) to block NO synthase. |
Methods |
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Instrumentation
Eleven mongrel dogs (average weight 32.4±1.0 kg) were anesthetized with sodium thiopental, intubated, and ventilated with room air mixed with halothane (1.2±0.2 vol%). Under sterile conditions, a left thoracotomy through the fifth intercostal space was performed. Tygon catheters (Norton Plastics) were implanted in the descending aorta and left atrium. Through an apical stab wound, a pressure transducer (model P7, Konigsberg Instruments) was implanted in the LV cavity. The circumflex coronary artery was isolated with minimal dissection, and a silastic catheter (0.30-mm ID, 0.63-mm OD; Dow Corning Co) was inserted into the proximal circumflex coronary artery. A 10-MHz Doppler flow probe was implanted around the circumflex artery distal to the tip of the intracoronary catheter. Two 5-MHz piezoelectric crystals attached on silk patches were sutured to the opposing surface of the circumflex artery near the Doppler flow probe to measure circumflex CD. A cuff occluder was placed around the circumflex artery upstream from the Doppler flow probe and CD crystals. The thoracic incision was closed in layers, and all wires and catheters were tunneled to the infrascapular area. Morphine (10 mg) was given subcutaneously when autonomic respiration had been restored in the dog. Postoperative care was made daily. Ampicillin (1 g/d) was given for 2 weeks. The intracoronary catheter was maintained patent with a continuous infusion of saline (Zyklomat BT1, Ferring SA) for 3 days. Thereafter, the catheter was flushed daily with heparinized saline. The animals used in the present study were maintained in accordance with the official regulations of the French Ministry of Agriculture.
Experimental Protocols
Experiments were initiated 3 to 6 weeks after surgery in
conscious healthy dogs. In 6 dogs, before any drug administration, a
blood sample was withdrawn by aortic catheter for hematological
analysis. After baseline hemodynamic
recordings, before drug injections, to verify the absence of
changes related to the injection method, a bolus of warm saline (0.2
mL) was injected into the circumflex artery and flushed with 0.5 mL
saline delivered with a pump-driven syringe over a 10-second period.
Then, by use of the same method, the dose-response curves of
des-Arg9-bradykinin (3, 10, 30, and 100 ng/kg)
and bradykinin (0.1, 1, 3, and 10 ng/kg; both from Sigma Chemical Co)
were established. In all experiments, saline solution (38°C) was
infused continuously at 1 mL/min. All drugs used were dissolved in warm
saline and freshly prepared before experiments. Between 2 injections, a
3-minute delay was allowed for 0.1 to 1 µg/kg bradykinin and 3 to 10
ng/kg des-Arg9-bradykinin, and a 15- to 30-minute
delay was allowed for 1 to 10 µg/kg bradykinin and 30 to 100 ng/kg
des-Arg9-bradykinin.
To determine the specificity of the response to bradykinin and des-Arg9-bradykinin, additional experiments were performed in 6 dogs after intracoronary infusion of a bradykinin B2 receptor antagonist, Hoe 140 (10 µg/kg infused in 1 minute; Icatibant, a kind gift of Dr B. Shölkens, Hoescht AG, Frankfurt, Germany). After baseline recordings, the responses to intracoronary bradykinin and des-Arg9-bradykinin were assessed.
To distinguish the flow-dependent phenomena and the direct effect of B1 or B2 receptor stimulation in the coronary diameter effect, the CD response to des-Arg9-bradykinin (100 ng/kg) and bradykinin (1 ng/kg) was examined before and after inflation of the coronary cuff occluder in 6 dogs.
To assess the influence of ACE inhibition on CBFv and CD responses to bradykinin and des-Arg9-bradykinin, intracoronary bradykinin and des-Arg9-bradykinin injections were repeated in 6 dogs after the administration of intracoronary lisinopril (0.75 mg, 1 mL/min for 5 minutes; ZENECA Pharma).
To determine the role of NO in the effects of B1 or B2 receptor stimulation, intracoronary des-Arg9-bradykinin and bradykinin injections were repeated in 6 dogs after pretreatment of LNA (2 mg/kg, 1 mL/min for 8 minutes).
To verify the constitutive existence of B1
receptors, 5 uninstrumented dogs were anesthetized with sodium
pentobarbital, and their hearts were removed. The circumflex artery was
isolated, cleaned of adherent connective tissue, and cut into rings
3 mm in length. In some rings, endothelium
removal was performed by rubbing the intimal layer with forceps. All
rings were suspended in organ chambers filled with 20 mL control
solution (modified Krebs-Ringer bicarbonate solution at 37°C) that
was gassed with 95% O2/5%
CO2 for isometric tension recording.
After pretreatment with bestatin (10 µm) and mergetpa (10
µmol/L) and 45 minutes of equilibration, rings were contracted with
thromboxane A2 analogue U46619
(1 µmol/L). Each ring was randomly assigned to either the
control solution or the B1 receptor
antagonist
des-Arg9-[Leu8]-bradykinin (10
µmol/L). Cumulative responses to increasing concentrations of
des-Arg9-bradykinin were obtained. The rings were
then washed with the control solution and contracted with U46619
(1 µmol/L), and relaxation to bradykinin (10 µmol/L) was
obtained in the presence of bestatin and mergetpa. Relaxations were
measured at peak decrease in tension for each concentration of drugs by
use of software from lOS-Laboratory (EMKA Technologies). Results are
expressed as percentage of the maximal contraction to U46619.
Data Collection and Analysis
Statham P23ID pressure transducers were used to measure aortic
and left atrial pressures. Absolute values of LV pressure were obtained
by calibration of the micromanometer in 37°C
water. CBFv was measured by a Doppler flowmeter (Triton Technology
Inc). CD was measured by a sonomicrometer (Triton
Instruments). The signals were monitored with an oscilloscope and
calibrated by the sonomicrometer. All signals were input
into a microcomputer with the use of Hem v1.5 software (Notocord
Systems) and monitored on a multitask graphic recorder.
Hemodynamic parameters were calculated at baseline and at peak increase in mean CBFv in response to various agents. The duration of CBFv and CD increases induced by bradykinin and des-Arg9-bradykinin was determined as the interval between the initial rise and the return to baseline CBFv and CD. At autopsy, the position, alignment, and orientation of the crystals were examined. The position of the intracoronary catheter was confirmed, and the coronary artery distal to the intracoronary catheter and the territory of left ventricle perfused by the circumflex artery were macroscopically examined.
Statistical Analysis
Values are expressed as mean±1 SEM. Experimental results were
subjected to an ANOVA for repeated measures (superANOVA, Abacus
Concepts, Inc). A 1-way ANOVA for repeated measurements was used for
intragroup interactions. A 2-way ANOVA for repeated measurements with
the same parameters was used for intergroup interactions.
When a significant trend was observed by variance analysis,
comparisons between means, such as the effects of the same dose of
bradykinin or des-Arg9-bradykinin before and
after lisinopril, LNA, or HOE 140 treatment, were performed
by contrast analysis. When only 2 means were compared, a paired
t test was used. A difference was considered statistically
significant at P<0.05.
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Results |
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At autopsy, macroscopic examination did not reveal any lesion in the catheterized circumflex artery or in the region of myocardium supplied by this vessel. Blood analysis at the beginning of the experimental protocol showed that erythrocytes (5.5±0.3x1012/L), hematocrit (38.7±2.2%), leukocytes (13.6±0.5x109/L), and fibrinogen (3.2±1 g/L) were within the normal range of values for dogs.
Coronary Effects of Bradykinin and
des-Arg9-Bradykinin
Baseline systemic and coronary parameters were
similar before the administration of bradykinin and
des-Arg9-bradykinin
(Table
). Intracircumflex injection of bradykinin
and des-Arg9-bradykinin did not modify heart
rate, mean arterial pressure, left ventricular
(LV) systolic and end-diastolic pressures, or LV
dP/dt max. Bradykinin and des-Arg9-bradykinin
increased dose-dependent CBF velocity (CBFv) and CD (Figure 1). However, the CBFv and CD increases
induced by des-Arg9-bradykinin were smaller than
those produced by bradykinin (P<0.05). The dose of 100
ng/kg des-Arg9-bradykinin produced changes in
CBFv and in CD similar to those produced by 1 ng/kg bradykinin (Figure 1).
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) in mean CBFv (top) and CD (bottom)
induced by intracoronary bradykinin (left) and
des-Arg9 bradykinin (right). Both agents dose-dependently
increased CBFv and CD, but des-Arg9-bradykinin was
significantly less potent than bradykinin. *P<0.05 vs
baseline.
Coronary Responses to Bradykinin and
des-Arg9-Bradykinin in the Presence of Hoe 140
Intracircumflex injection of Hoe 140 did not produce any change in
systemic hemodynamics, CBFv, or CD. After the injection
of Hoe 140, bradykinin and des-Arg9-bradykinin
did not modify systemic hemodynamics. Pretreatment with
Hoe 140 markedly and significantly decreased CBFv and CD responses to
bradykinin but did not alter CBFv and CD responses to
des-Arg9-bradykinin (Figure 2).
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P<0.05 vs absence of Hoe 140.
CD Response to Bradykinin and des-Arg9-Bradykinin Under
Controlled CBFv
Inflation of the coronary cuff occluder did not modify
baseline systemic hemodynamics but decreased baseline
mean CBFv and CD (from 18±2 to 15±3 cm/s and from 3324±259 to
3258±239 µm, respectively; P<0.05). When the
increase in CBFv was prevented, the CD response was not different from
that obtained before inflation of the coronary cuff occluder
(Figure 3), suggesting that the CD
responses to des-Arg9-bradykinin and bradykinin
were not flow dependent.
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Coronary Responses to Bradykinin and
des-Arg9-Bradykinin in the Presence of Lisinopril
Lisinopril did not produce significant changes in
systemic hemodynamics, CBFv, or CD. After the
administration of lisinopril, intracoronary
bradykinin or des-Arg9-bradykinin did not change
systemic hemodynamics at any dose.
Lisinopril did not modify the peak response of CBFv to
bradykinin but significantly increased the peak response of CD (Figures 4 and 5,
top left panels) and prolonged the duration of CBFv and CD responses
(Figures 4 and 5, bottom left panels), indicating that
ACE inhibitors could affect the coronary response
to bradykinin. In contrast, lisinopril did not affect the
CBFv and CD effects of des-Arg9-bradykinin
(Figures 4 and 5, right panels).
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Coronary Responses to Bradykinin and
des-Arg9-Bradykinin After Pretreatment With LNA
LNA (2 mg/kg) did not produce any significant changes in systemic
hemodynamics other than a slight but significant
decrease in heart rate (from 81±5 to 72±2 bpm). LNA did not
significantly modify mean CBFv but decreased CD (from 3375±359 to
3279±352 µm, P<0.05). The peak effect of bradykinin
on mean CBFv tended to decrease and the peak effect on CD decreased
after LNA pretreatment (P<0.05; Figure 6, left panels), confirming the role of
NO in the coronary vasodilator effect of bradykinin. After LNA
pretreatment, des-Arg9-bradykinin did not modify
systemic hemodynamics. The effects of
des-Arg9-bradykinin on CBFv and CD were prevented
by LNA (Figure 6, right panels), indicating the implication of
NO in the coronary effects of
des-Arg9-bradykinin.
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In Vitro Coronary Responses to
des-Arg9-Bradykinin
The successive contractions of rings to U46619 were of similar
magnitude (16.2±1.6 g). des-Arg9-bradykinin
induced a concentration-dependent relaxation that was
endothelium dependent (Figure 7).
des-Arg9-[Leu8]-bradykinin
markedly reduced the des-Arg9-bradykinin–induced
relaxation. The bradykinin-induced relaxation was 5-fold larger than
that induced by des-Arg9-bradykinin and was not
altered by
des-Arg9-[Leu8]-bradykinin
(Figure 7).
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Discussion |
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The principal results of the present study show that in conscious dogs, intracoronary injection of des-Arg9-bradykinin, a bradykinin B1 receptor agonist, produces a dose-dependent coronary vasodilation in both conductance and resistance vessels. However, des-Arg9-bradykinin is less potent than bradykinin in coronary vessels, and in contrast to bradykinin, these coronary effects are not affected by bradykinin B2 receptor blockade or by ACE inhibition. In addition, NO synthase blockade prevents the coronary vasodilator effect of des-Arg9-bradykinin.
The present study provides the first evidence that under physiological conditions (distant from anesthesia and acute surgical trauma), coronary vasodilation in both conductance and resistance vessels produced by intracoronary des-Arg9-bradykinin is mediated by bradykinin B1 receptors. This is supported by the fact that Hoe 140, a selective B2 receptor antagonist,16 17 did not block the effects of des-Arg9-bradykinin and that this effect was blocked in vitro by a B1 receptor antagonist, des-Arg9,[Leu8]-bradykinin. In anesthetized greyhounds, intracoronary injection of a small dose of des-Arg9-bradykinin increased CBFv but did not modify CD, whereas a larger dose of des-Arg9-bradykinin increased both CBFv and CD in association with systemic effects.18 In this latter study,18 the question of whether the CD response was receptor- or flow-mediated was unresolved. The present study performed in conscious dogs, in the absence of systemic effects, shows that the CD increase in response to des-Arg9-bradykinin was essentially due to B1 receptor stimulation rather than a flow-dependent phenomenon because CBF limitation by inflating a coronary cuff occluder did not affect the CD response to des-Arg9-bradykinin.
Normal vessels from most animal species are generally considered to be constitutively lacking bradykinin B1 receptors. However, B1 receptors are heterogeneously expressed depending on species and tissues.7 In normal rats, intra-arterial injections of des-Arg9-bradykinin produce weak but measurable hemodynamic responsiveness, and the B1 receptor antagonist des-Arg9-[Leu8]-bradykinin reduces the glomerular filtration rate and urine concentration, suggesting the presence of constitutive B1 receptors in the arterial trees and in the kidneys of rats.8 9 In pigs, des-Arg9-bradykinin also produces measurable hypotensive effects.11 In cats, the pulmonary vascular bed contains functional B1 receptors; the stimulation of these receptors produces tone-dependent changes in pulmonary artery pressure.10 In dogs, B1 receptors are also present in the isolated renal artery and mediate vasorelaxation,12 and in intact preparations, B1 receptor stimulation by des-Arg9-bradykinin produces a hypotensive effect.13 14 By use of a specific antibody directed to the peptide sequences of B1 receptors, it has recently been shown in humans that B1 receptors are present not only in vascular endothelial and smooth muscle cells of large elastic arteries but also in muscular arteries, such as coronary arteries and muscular arterioles.15 The notion that B1 receptors are constitutively expressed in coronary vessels is supported by the present study, which shows the functional coronary effects of des-Arg9-bradykinin in the absence of evidence of inflammation by blood analysis. Although bradykinin can be metabolized into des-Arg9-bradykinin in dogs, the lack of effects of bradykinin through B1 receptor stimulation after Hoe 140 pretreatment that we observed may be related to the fact that injected doses of bradykinin were lower than the dose of des-Arg9-bradykinin producing any significant effect. Finally, in coronary rings obtained from uninstrumented dogs, des-Arg9-bradykinin produced a concentration-dependent relaxation.
Several studies have shown that NO is involved in the relaxing effect of kinins.19 20 In the present study, pretreatment with LNA significantly decreased the peak response of CD to bradykinin but only slightly decreased the CBFv response. The minimal influence of LNA on the CBFv response is consistent with that reported in porcine coronary resistance arteries.21 This CBFv response to bradykinin, which is resistant to inhibitors of NO synthase, may be mediated by endothelium-derived hyperpolarizing factor (EDHF), because it has been shown that the relaxing response of coronary vessels to bradykinin is also mediated by EDHF, which probably acts through calcium-activated potassium channels.22 23 However, the in vivo role of EDHF remains unknown because EDHF has not been identified. The coronary effects of des-Arg9-bradykinin on conductance and resistance vessels were prevented by LNA, indicating that the effects of des-Arg9-bradykinin are, in a large part, mediated by NO, which is consistent with a previous study in which NO synthase inhibitors and des-Arg9-bradykinin were administrated intravenously.13
In vitro, the bradykinin-induced vasorelaxation is potentiated by ACE inhibitors.24 In humans, bradykinin is involved in the vascular effect of ACE inhibitors.25 A recent study from our laboratory has shown that enalaprilat extends the duration of the effect of bradykinin with no significant changes in the peak CBFv response to bradykinin.26 The present study, using lisinopril, demonstrates a similar result in association with an increased CD response to bradykinin. However, lisinopril did not modify the coronary responses to des-Arg9-bradykinin, which is in accordance with observations in the pulmonary circulation of cats,10 indicating that in the coronary circulation in vivo, ACE plays only a small role in des-Arg9-[Leu8]-bradykinin metabolism. Although it has been shown in vitro that ACE inhibitors may prevent the degradation of des-Arg9-bradykinin,27 an in vivo experiment did not find an increased blood concentration of des-Arg9-bradykinin after enalapril administration.28 This may explain why ACE inhibitors do not influence the effects of des-Arg9-bradykinin.
Previous in vitro and in vivo studies have shown that B2 receptors mediate the major physiological effects of kinins.19 29 Our data indicating that bradykinin is more potent than des-Arg9-bradykinin in conductance and resistance coronary vessels support this notion. However, the possible role of B1 receptors under pathological circumstances remains to be investigated because the plasma concentration of des-Arg9-bradykinin is higher than that of bradykinin in patients with hypertension28 and because B1 receptors can be upregulated and exhibit less desensitization than do B2 receptors,30 which may lead to a predominant effect of B1 receptors. In human coronary vessels, as previously mentioned, B1 receptors are present and can be upregulated, with their in vitro stimulation producing a vasorelaxing effect.31 In addition, a recent study reports that B1 receptors are more abundant than B2 receptors in atheromatous plaques of human coronary vessels, suggesting that B1 receptors may be involved in atheromatous disease.15
In conclusion, the present study shows for the first time that under physiological conditions, bradykinin B1 receptors are functionally present in canine coronary vessels and that their stimulation produces vasodilation in conductance and resistance vessels that is mediated in large part by NO and is not modulated by ACE inhibition. Although the coronary vasodilation induced by B1 receptor stimulation is less potent than that produced by B2 receptor stimulation under physiological conditions, the stimulation of B1 receptors may exert potent vasoactive coronary effects in pathological conditions (such as local or systemic inflammation and sepsis) in which B1 receptors can be upregulated.
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Acknowledgments |
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This study was supported in part by a grant from ZENECA Pharma (Cergy, France).
Received June 15, 1999; revision received October 27, 1999; accepted November 11, 1999.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Regoli D, Barabé J. Pharmacology of bradykinin and related kinins. Pharmacol Rev. 1980;32:1–46.[Medline] [Order article via Infotrieve]
2. Hess JF, Borkowski JA, Young GS, Strader CD, Ransom RW. Cloning and pharmacological characterization of a human bradykinin (BK2) receptor. Biochem Biophys Res Commun. 1992;184:260–268.[Medline] [Order article via Infotrieve]
3.
Menke JG, Borkowski JA, Bierilo KK, MacNeil T,
Derrick AW, Sheneck KA, Ransom RW, Strader CD, Linemeyer DL, Hess JF.
Expression cloning of a human bradykinin receptor. J Biol
Chem. 1994;269:21583–21586.
4. Deblois D, Bouthillier J, Marceau F. Pulse exposure to protein synthesis inhibitors enhances tissue response to des-Arg9-bradykinin: possible role of interleukin-1. Br J Pharmacol. 1991;103:1057–1066.[Medline] [Order article via Infotrieve]
5. Regoli D, Marceau F, Lavigne J. Induction of B1 receptors for kinins in the rabbit by a bacterial lipopolysaccharide. Eur J Pharmacol. 1981;105–115.
6. Bouthillier J, Deblois D, Marceau F. Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo. Br J Pharmacol. 1987;92:257–264.[Medline] [Order article via Infotrieve]
7.
Wohlfart P, Denio J, Wirth K, Schölkens
BA, Wiemer G. Different B1 receptor expression
and pharmacology in endothelial cells of different
origins and species. J Pharmacol Exp Ther. 1997;280:1109–1118.
8. Madeddu P, Emanueli, C, Varoni MV, Demontis MP, Anania V, Gorioso N, Chao J. Regulation of bradykinin B2 receptor expression by oestrogen. Br J Pharmacol. 1997;121:1763–1769.[Medline] [Order article via Infotrieve]
9.
Fenoy FJ, Roman RJ. Effect of kinin receptor
antagonists on renal hemodynamic and
natriuretic responses to volume expansion. Am J
Physiol. 1992;263:R1136–R1140.
10.
DeWitt BJ, Cheng DY, Kadowitz PJ.
Des-Arg9-bradykinin produces tone-dependent kinin
B1 receptor–mediated responses in the
pulmonary vascular bed. Circ Res. 1994;75:1064–1072.
11. Siebeck M, Whally ET, Hoffmann H, Weipert J, Fritz H. The hypotensive response to des-Arg9-bradykinin increases during E. coli septicemia in the pig. Adv Exp Med Biol. 1989;247B:389–393.
12. Rhaleb NE, Dion S, Barabé J, Roussi N, Jukic D, Drapeau G, Regoli D. Receptors of kinins in isolated arterial vessels of dogs. Eur J Pharmacol. 1989;162:419–427.[Medline] [Order article via Infotrieve]
13. Bélichard P, Loillier B, Paquet JL, Luccartini JM, Pruneau D. Haemodynamic and cardiac effects of kinin B1 and B2 receptor stimulation in conscious instrumented dogs. Br J Pharmacol. 1996;117:1565–1571.[Medline] [Order article via Infotrieve]
14. Nakhostine N, Ributo C, Lamontagne D, Nadeau R, Couture R. Mediation by B1 and B2 receptors of vasodepressor responses to intravenously administered kinins in anaesthetized dogs. Br J Pharmacol. 1993;110:71–76.[Medline] [Order article via Infotrieve]
15. Raidoo DM, Ramsaroop R, Naidoo S, Müller-Esterl W, Bhoola KD. Kinin receptors in human vascular tissue: their role in atheromatous disease. Immunopharmacology. 1997;36:153–160.[Medline] [Order article via Infotrieve]
16.
Marceau F, Hess JF, Bachvarov D. The B1 receptors
for kinins. Pharmacol Rev. 1998;50:357–386.
17. Regoli D, Nsa Allogho S, Rizzi A, Gobeil FJ. Bradykinin receptors and their antagonists. Eur J Pharmacol. 1998;348:1–10.[Medline] [Order article via Infotrieve]
18. Staszewska-Woolly J, Woodman OL. Kinin receptors mediating the effects of bradykinin on the coronary circulation in anaesthetized greyhounds. Eur J Pharmacol. 1991;196:9–14.[Medline] [Order article via Infotrieve]
19.
Pelc LR, Gross GJ, Warltier DC. Mechanism of
coronary vasodilation produced by bradykinin.
Circulation. 1991;83:2048–2056.
20. Mombouli JV, Vanhoutte PM. Kinins and endothelial control of vascular smooth muscle. Annu Rev Pharmacol Toxicol. 1995;35:679–705.[Medline] [Order article via Infotrieve]
21.
Tschudi M, Richard V, Bühler FR,
Lüscher TF. Importance of endothelium-derived
nitric oxide in porcine coronary resistance arteries.
Am J Physiol. 1991;260:H13–H20.
22.
Miura H, Liu Y, Gutterman DD. Human
coronary arteriolar dilation to bradykinin depends on membrane
hyperpolarization: contribution of nitric oxide and
Ca2+-activated K+
channels. Circulation. 1999;99:3132–3138.
23.
Thollon C, Bidouard JP, Cambarrat C, Delescluse
I, Villeneuve N, Vanhoutte PM, Vilaine JP. Alteration of
endothelium-dependent
hyperpolarizations in porcine coronary
arteries with regenerated endothelium. Circ
Res. 1999;84:371–377.
24.
Mombouli JV, Illiano S, Nagao T, Scott-Burden T,
Vanhoutte PM. Potentiation of endothelium-dependent
relaxation to bradykinin by angiotensin I converting enzyme
inhibitors in canine coronary artery involves both
endothelium-derived relaxing and hyperpolarizing
factors. Circ Res. 1992;71:137–144.
25.
Hornig B, Lohler C, Drexler H. Role of bradykinin
in mediating vascular effects of angiotensin-converting
enzyme inhibitors in humans. Circulation. 1997;95:1115–1118.
26. Hoüel R, Su J, Barbe F, Choussat R, Crozatier B, Hittinger L. Regional myocardial effects of intracoronary bradykinin in conscious dogs. Am J Physiol. 1997;272:H1296–H1274.
27. Décarie A, Raymond P, Gervais N, Couture R, Adam A. Serum interspecies differences in metabolic pathways of bradykinin and [des-Arg9]BK: influence of enalaprilat. Am J Physiol. 1996;270:H1340–H1347.
28. Odya CE, Wilgis FP, Walker JF, Oparil S. Immunoreactive bradykinin and [des-Arg9]-bradykinin in low-renin essential hypertension before and after treatments with enalapril (MK-421). J Lab Clin Med.. 1983;102:714–721.[Medline] [Order article via Infotrieve]
29.
Minshall RD, Yelamanchi VP, Djokovic A, Miletich
DJ, Erdös EG, Rabito SF, Vogel SM. Importance of sympathetic
innervation in the positive inotropic effects of bradykinin and
ramiprilat. Circ Res. 1994;74:441–447.
30.
Austin CE, Faussner A, Robinson HE, Chakravarty
S, Kyle DJ, Bathon JM, Proud D. Stable expression of the human kinin B1
receptors in Chinese hamster ovary cells: characterization of ligand
binding and effector pathways. J Biol Chem. 1997;272:11420–11425.
31. Drummond GR, Cocks TM. Endothelium-dependent relaxation to B1 receptor agonist des-Arg9-bradykinin in human coronary arteries. Br J Pharmacol. 1995;116:3083–3085.[Medline] [Order article via Infotrieve]
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