QUINAPRILAT INDUCES ARTERIAL VASODILATION MEDIATED BY NITRIC-OXIDE INHUMANS

The beneficial therapeutic effects of angiotensin-converting enzyme (A CE) 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-pene trating properties, such as quinaprilat, may exert vascular effects vi a the bradykinin B-2-receptor. To test direct arterial effects of quin aprilat and enalaprilat and to study their effects on vasodilation ind uced by bradykinin, venous occlusion plethysmography was used during l ocal intra-arterial drug administration into the brachial artery in he althy volunteers. The response to bradykinin was augmented by both ACE inhibitors, but the effect of quinaprilat (3.9 nmol/min) was exclusiv ely attributable to its direct vasodilator action. Enalaprilat (13 nmo l/min) did not change baseline blood flow in the human forearm circula tion. In contrast, quinaprilat significantly increased arterial flow f rom 3.5+/-0.5 to 4.6+/-0.7 mL/100 mL tissue/min, which was inhibited b y N-G-monomethyl-L-arginine (8 mu mol/min IA). Moreover, the effect of sodium nitroprusside (0.023 to 22.9 nmol/min) was substantially atten uated during concomitant administration of quinaprilat. These results suggest that quinaprilat induces vascular effects beyond the inhibitio n of angiotensin II formation; it causes vasodilation by increasing va scular nitric oxide production and thereby attenuates the relaxing eff ect of the nitric oxide donor sodium nitroprusside.