Quinaprilat induces arterial vasodilation mediated by nitric oxide in humans.
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 micromol/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.
Haefeli
W E
WE
Department of Internal Medicine, University Hospital, University of Basel, Switzerland. haefeli@ubaclu.unibas.ch
Linder
L
L
Lüscher
T F
TF
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D044005:Tetrahydroisoquinolines; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C054501:quinaprilat; D001920:Bradykinin