Circulation, Vol 87, 931-938, Copyright © 1993 by American Heart Association
K Sudhir, JS MacGregor, M Gupta, SD Barbant, R Redberg, PG Yock and K Chatterjee
BACKGROUND. Although angiotensin converting enzyme (ACE) inhibitors have
been reported to increase coronary blood flow, the effect of selective
angiotensin II (AT1)-receptor antagonism on the coronary circulation has
not been defined. METHODS AND RESULTS. We examined the effects of the
AT1-receptor antagonist Losartan (DuP 753, 0.2-3.2 mg/kg) on coronary
arteries in vivo in 11 dogs, using a combination of intravascular
two-dimensional and Doppler ultrasound. In six dogs, a 30- MHz, 4.3F
ultrasound imaging catheter was placed in the midsegment of the circumflex
coronary artery to measure cross-sectional area (CSA), and a 0.018-in.
Doppler wire was placed alongside to measure coronary flow velocity. At
peak effect (1.6 mg/kg), Losartan increased mean coronary CSA from 7.9 +/-
0.5 to 9.5 +/- 0.8 mm2 and average peak velocity (APV) from 32 +/- 10 to 56
+/- 18 cm/sec, resulting in an increase in coronary blood flow from 74 +/-
19 to 151 +/- 36 mL/min. The maximal effect of the ACE inhibitor
enalaprilat (5 mg) was an increase in CSA from 7.7 +/- 0.7 to 8.4 +/- 0.8
mm2 and an increase in APV from 36 +/- 10 to 53 +/- 20 cm/sec, with an
increase in coronary blood flow from 82 +/- 25 to 122 +/- 41 mL/min.
Relative to maximal hyperemia with adenosine (6 mg i.c.), the magnitude of
flow increase from baseline was 0.37 with the AT1-receptor antagonist and
0.19 with the ACE inhibitor (p < 0.05). These effects were seen without
changes in heart rate or systemic arterial pressure. In an additional five
dogs, the ultrasound imaging catheter was introduced directly over a
0.014-in. Doppler wire, and the effects of indomethacin, propranolol, and N
omega-nitro-L-arginine methylester (L-NAME) on the vasodilator effect of
Losartan (1.6 mg/kg) were examined. Indomethacin and propranolol had no
effect on Losartan-induced vasodilation, suggesting that it was not
mediated via prostaglandins or beta-adrenoceptors. However,
Losartan-induced epicardial vasodilation was partially inhibited by L-NAME,
suggesting an action partly dependent on endothelial release of nitric
oxide. CONCLUSIONS. Thus, these acute studies in anesthetized dogs suggest
that inhibition of AT1-receptors in the coronary circulation results in
vasodilator responses greater in magnitude than ACE inhibition and partly
endothelium dependent. The exact role for AT1-receptors in human coronary
physiology and pathology remains to be defined.
ARTICLES
Effect of selective angiotensin II receptor antagonism and angiotensin converting enzyme inhibition on the coronary vasculature in vivo. Intravascular two-dimensional and Doppler ultrasound studies
Cardiovascular Research Institute, University of California, San Francisco 94143.
This article has been cited by other articles:
 |
|
 |
|
  M. White, H. Ross, S. Levesque, L. Whittom, G. B Pelletier, N. Racine, S. Meloche, and L. Voisin Effects of Angiotensin-Converting Enzyme Inhibitor Versus Valsartan on Cellular Signaling Events in Heart Transplant Ann. Pharmacother., May 1, 2009; 43(5): 831 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Toda, K. Ayajiki, and T. Okamura Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation Pharmacol. Rev., March 1, 2007; 59(1): 54 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Merkus, D. B. Haitsma, O. Sorop, F. Boomsma, V. J. de Beer, J. M. J. Lamers, P. D. Verdouw, and D. J. Duncker Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2082 - H2089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zhang, J. D. Knudson, S. Setty, A. Araiza, U. D. Dincer, L. Kuo, and J. D. Tune Coronary arteriolar vasoconstriction to angiotensin II is augmented in prediabetic metabolic syndrome via activation of AT1 receptors Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2154 - H2162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Hornig, C. Kohler, D. Schlink, H. Tatge, and H. Drexler AT1-Receptor Antagonism Improves Endothelial Function in Coronary Artery Disease by a Bradykinin/B2-Receptor-Dependent Mechanism Hypertension, May 1, 2003; 41(5): 1092 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zhang, T. W. Hein, W. Wang, and L. Kuo Divergent Roles of Angiotensin II AT1 and AT2 Receptors in Modulating Coronary Microvascular Function Circ. Res., February 21, 2003; 92(3): 322 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Prasad, J. P. J. Halcox, M. A. Waclawiw, and A. A. Quyyumi Angiotensin type 1 receptor antagonism reverses abnormal coronary vasomotion in atherosclerosis J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1089 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Oikawa, K. Maehara, T. Saito, K. Tamagawa, and Y. Maruyama Attenuation of angiotensin II-mediated coronary vasoconstriction and vasodilatory action of angiotensin-converting enzyme inhibitor in pacing-induced heart failure in dogs J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1188 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Hornig, U. Landmesser, C. Kohler, D. Ahlersmann, S. Spiekermann, A. Christoph, H. Tatge, and H. Drexler Comparative Effect of ACE Inhibition and Angiotensin II Type 1 Receptor Antagonism on Bioavailability of Nitric Oxide in Patients With Coronary Artery Disease : Role of Superoxide Dismutase Circulation, February 13, 2001; 103(6): 799 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Prasad, T. Tupas-Habib, W. H. Schenke, R. Mincemoyer, J. A. Panza, M. A. Waclawin, S. Ellahham, and A. A. Quyyumi Acute and Chronic Angiotensin-1 Receptor Antagonism Reverses Endothelial Dysfunction in Atherosclerosis Circulation, May 23, 2000; 101(20): 2349 - 2354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Anderson, E. Elstein, H. Haber, and F. Charbonneau Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study) J. Am. Coll. Cardiol., January 1, 2000; 35(1): 60 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Schneider, E. Voth, D. Moka, F. M. Baer, J. Melin, A. Bol, R. Wagner, H. Schicha, E. Erdmann, and U. Sechtem Improvement of myocardial blood flow to ischemic regions by angiotensin- converting enzyme inhibition with quinaprilat IV: A study using [15O] water dobutamine stress positron emission tomography J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1005 - 1011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Anderson Assessment and treatment of endothelial dysfunction in humans J. Am. Coll. Cardiol., September 1, 1999; 34(3): 631 - 638. [Full Text] [PDF]
|
|
|
|
 |
|
 R.S. Krombach, M. J Clair, J. W Hendrick, W. V Houck, J. L Zellner, S. B Kribbs, S. Whitebread, R. Mukherjee, M. de Gasparo, and F. G Spinale Angiotensin converting enzyme inhibition, AT1 receptor inhibition, and combination therapy with pacing induced heart failure: effects on left ventricular performance and regional blood flow patterns Cardiovasc Res, June 1, 1998; 38(3): 631 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kyriakidis, F. Triposkiadis, J. Dernellis, A. E. Androulakis, P. Mellas, G. A. Kelepeshis, and J. E. Gialafos Effects of Cardiac Versus Circulatory Angiotensin-Converting Enzyme Inhibition on Left Ventricular Diastolic Function and Coronary Blood Flow in Hypertrophic Obstructive Cardiomyopathy Circulation, April 14, 1998; 97(14): 1342 - 1347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Rongen, S. C. Brooks, S.-i. Ando, H. R. Dajani, B. L. Abramson, and J. S. Floras Neural and Hypotensive Effects of Angiotensin II Receptor Blockade Hypertension, January 1, 1998; 31(1): 378 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sudhir, E. Ko, C. Zellner, H. E. Wong, S. J. Hutchison, T. M. Chou, and K. Chatterjee Physiological Concentrations of Estradiol Attenuate Endothelin 1–Induced Coronary Vasoconstriction In Vivo Circulation, November 18, 1997; 96(10): 3626 - 3632. [Abstract] [Full Text]
|
|
|
|
|
|
K. Sudhir, T. M. Chou, S. J. Hutchison, and K. Chatterjee Coronary Vasodilation Induced by Angiotensin-Converting Enzyme Inhibition In Vivo : Differential Contribution of Nitric Oxide and Bradykinin in Conductance and Resistance Arteries Circulation, May 1, 1996; 93(9): 1734 - 1739. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. Kovach, J. S. Gottdiener, and R. L. Verrier Vagal Modulation of Epicardial Coronary Artery Size in Dogs : A Two-Dimensional Intravascular Ultrasound Study Circulation, October 15, 1995; 92(8): 2291 - 2298. [Abstract] [Full Text]
|
|