ABSTRACT
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.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Enalaprilat/pharmacology , Forearm/blood supply , Hypertension/physiopathology , Isoquinolines/pharmacology , Tetrahydroisoquinolines , Vasodilation/drug effects , Aged , Angiotensin II/blood , Blood Pressure/drug effects , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Heart Rate/drug effects , Humans , Male , Middle Aged , Peptidyl-Dipeptidase A/blood , Regional Blood Flow/drug effectsABSTRACT
OBJECTIVE: Infusion of ANP in anephric dogs causes a decrease in cardiac output and a rise in peripheral vascular resistance. This reduced cardiac output is possibly related to increased resistance to venous return generated in the microcirculation by venular constriction. The aim of the present study was to evaluate in healthy volunteers the effects of low-dose ANP infusion on both conjunctival and skin microcirculation during high or low salt diet. METHODS: ANP (7.5 ng/kg/min) and placebo were infused (i.v.) for 4 h, in random order on two separate days, in two groups of 10 healthy male volunteers each. One group was studied during high salt (ad libitum), and one group during low salt (55 mmol Na+/24 h) diet. Microvascular density and diameters of both conjunctiva and nailfold were studied using intravital videomicroscopy. Nailfold capillary red blood cell velocity (CBV) was studied using intravital videomicroscopy, and skin (thermoregulatory) blood flow (SBF) was studied using laser-Doppler fluximetry. RESULTS: In the high salt group ANP induced a 43% reduction in basal SBF as compared to an 18% reduction by placebo (P < 0.01). Parallel to SBF, ANP significantly reduced CBV (P < 0.02). Conjunctival capillary density decreased by 5% during ANP, while it increased by 28% during placebo (P < 0.05). No such effects of ANP were observed in the low salt group. Blood pressure and heart rate were not influenced by ANP infusion in neither group. CONCLUSION: Infusion of low doses of ANP into humans on an ad libitum salt diet results in vasoconstriction of the microcirculation, probably on the venular side. The lack of effect of ANP on the microcirculation during low salt diet may be related to a higher vascular tone prior to infusion.
