Quinaprilat-induced vasodilatation in forearm vasculature of patients with essential hypertension: comparison with enalaprilat.
The aim of the present study was to assess the possible differences in hemodynamic and neurohumoral responses to local ACE inhibition in the human forearm of patients with essential hypertension with either quinaprilat or enalaprilat. Forearm vascular responses to infusion of quinaprilat or enalaprilat (0.5 microg/dL/min) into the brachial artery were studied in 12 male patients with essential hypertension. The experiments were performed in a randomized, double-blind, crossover fashion. Before and during ACE inhibition, the vasoconstrictor response to four cumulative doses of angiotensin I (Ang I) was studied. Forearm blood flow was assessed using venous occlusion plethysmography. Local quinaprilat infusion induced a more rapid (even after 15 minutes; median vasodilation quinaprilat 29% vs. enalaprilat --1%, P < 0.02) and longer lasting forearm vasodilation as compared with enalaprilat. After 15 minutes of local ACE inhibition, the vasoconstrictor response to Ang I was completely blocked by both ACE inhibitors. We conclude that in patients with essential hypertension quinaprilat induces a more rapid and longer lasting vasodilatation than enalaprilat. These effects of quinaprilat are possibly related to its higher affinity for vascular ACE. On the other hand, the fact that these effects of quinaprilat were observed despite a similar degree of ACE inhibition as during enalaprilat may suggest that quinaprilat directly stimulates another vasodilatating mechanism.
Houben
A J
AJ
Department of Internal Medicine, University Hospital Maastricht, The Netherlands. BHO@sint.azm.nl
Kroon
A A
AA
de Haan
C H
CH
Fuss-Lejeune
M J
MJ
de Leeuw
P W
PW
D000368:Aged; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015773:Enalaprilat / Q000494:pharmacology*; D005542:Forearm / Q000098:blood supply*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects; D044005:Tetrahydroisoquinolines; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; C054501:quinaprilat; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat