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(Hypertension. 1997;30:912-917.)
© 1997 American Heart Association, Inc.

Articles

Quinaprilat Induces Arterial Vasodilation Mediated by Nitric Oxide in Humans

Walter E. Haefeli; Lilly Linder; ; Thomas F. Lüscher

From the Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital, CH-4031 Basel, Switzerland (W.E.H., L.L.); the Department of Pharmacy, University of Basel, CH-4051 Basel, Switzerland (W.E.H.); and the Division of Cardiology, University Hospital/CH-8091 Zürich, Switzerland (T.F.L.).

Correspondence to Walter E. Haefeli, MD, Division of Clinical Pharmacology, Department of Medicine, University Hospital, Petersgraben 4, CH-4031 Basel, Switzerland. E-mail haefeli{at}ubaclu.unibas.ch

Abstract The beneficial therapeutic effects of angiotensin-converting enzyme (ACE) inhibitors are the result of reduced angiotensin II formation and possibly also of an accumulation of bradykinin that is inactivated by ACE. In particular, recently developed ACE inhibitors with tissue-penetrating properties, such as quinaprilat, may exert vascular effects via the bradykinin B₂-receptor. To test direct arterial effects of quinaprilat and enalaprilat and to study their effects on vasodilation induced by bradykinin, venous occlusion plethysmography was used during local intra-arterial drug administration into the brachial artery in healthy volunteers. The response to bradykinin was augmented by both ACE inhibitors, but the effect of quinaprilat (3.9 nmol/min) was exclusively attributable to its direct vasodilator action. Enalaprilat (13 nmol/min) did not change baseline blood flow in the human forearm circulation. In contrast, quinaprilat significantly increased arterial flow from 3.5±0.5 to 4.6±0.7 mL/100 mL tissue/min, which was inhibited by N^G-monomethyl-L-arginine (8 µmol/min IA). Moreover, the effect of sodium nitroprusside (0.023 to 22.9 nmol/min) was substantially attenuated during concomitant administration of quinaprilat. These results suggest that quinaprilat induces vascular effects beyond the inhibition of angiotensin II formation; it causes vasodilation by increasing vascular nitric oxide production and thereby attenuates the relaxing effect of the nitric oxide donor sodium nitroprusside.

Key Words: bradykinin • angiotensin-converting enzyme inhibition • nitric oxide • vasodilation • vascular resistance

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