(Circulation. 1996;93:1734-1739.)
© 1996 American Heart Association, Inc.
Articles |
Coronary Vasodilation Induced by Angiotensin-Converting Enzyme Inhibition In Vivo
Differential Contribution of Nitric Oxide and Bradykinin in Conductance and Resistance Arteries
From the Cardiovascular Research Institute and Division of Cardiology, University of California at San Francisco.
Correspondence to K. Sudhir, MD, PhD, Box 0124, University of California at San Francisco, 505 Parnassus Ave, San Francisco, CA 94143-0124. E-mail sudhir@cardio.ucsf.edu.
Background We studied in coronary conductance and resistance arteries the coronary vasodilator effects of the angiotensin-converting enzyme inhibitor ramiprilat and the contribution of nitric oxide, bradykinin, and prostaglandins to this vasodilation.
Methods and Results In seven anesthetized dogs, a
Doppler guidewire was placed in the circumflex coronary
artery to measure coronary flow velocity, and an ultrasound
imaging catheter was introduced over the Doppler wire to measure
coronary cross-sectional area. Drugs were infused directly
into the left main coronary artery to minimize systemic
effects. Ramiprilat increased both epicardial
cross-sectional area and coronary blood flow velocity,
resulting in an increase in absolute coronary blood flow.
Pretreatment with
N
-nitro-L-arginine methyl ester
(100 µmol/L intracoronary) to block nitric oxide synthase
attenuated ramiprilat-induced increase in epicardial
coronary cross-sectional area (P<.05) but not
in coronary flow velocity or coronary blood flow. In
contrast, pretreatment with the selective bradykinin
antagonist HOE 140 (10 µmol/L) attenuated
ramiprilat-induced increase in flow velocity
(P<.025) and coronary blood flow
(P<.05) but not epicardial coronary
cross-sectional area. Pretreatment with
indomethacin (5 mg/kg body wt IV) did not alter
ramiprilat-induced increase in epicardial
cross-sectional area, nor did it significantly influence
coronary blood flow.
Conclusions Other than decreasing angiotensin II production, acute ramiprilat-induced vasodilation in canine coronary conductance arteries is mediated in part by nitric oxide. Ramiprilat-induced vasodilation in resistance arteries is in part mediated by the action of bradykinin.
Key Words: angiotensin • blood flow • bradykinin • endothelium-derived factors
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