Vascular effects of intravenous infusion of the angiotensin converting enzyme inhibitor perindoprilat

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Abstract
This study was aimed at evaluating the hemodynamic changes after acute inhibition of the renin-angiotensin system in hypertensive patients. Twenty-one subjects with essential hypertension were randomized into three groups of seven subjects each. In group I, the direct vascular vasodilator dihydralazine was administered at a dose of 4 .mu.g/kg per min. Groups II and III received a continuous intravenous infusion of the angiotensin converting enzyme (ACE) inhibitor perindoprilat at a dose of 1 .mu.g/kg per min and 2.5 .mu.g/kg per min, respectively. Brachial artery hemodynamics and aortic distensibility were evaluated non-invasively. Vascular reactivity was evaluated by the cold-pressor test. In all three groups, an identical decrease in blood pressure was observed (P < 0.001), followed by a slight (but not significant) decrease in the heart rate in both perindoprilat groups, and an important tachycardia in the dihydralazine group (P < 0.001). Brachial artery diameter was increased in the high-dose perindoprilat group from 0.437 .+-. 0.014 to 0.479 .+-. 0.013 cm (P < 0.02), but remained unchanged in the two other groups. No significant changes in brachial artery mean blood velocity and blood flow were observed. In group III, aortic distensibility increased almost twice as much as in the two other groups, but this difference was not statistically significant. The pressor response to the cold-pressor test was not modified in the three groups, the heart rate response was almost completely abolished in groups II and III, but increased in the dihydralazine group (P < 0.01). These results suggest that (1) intravenous administration of perindoprilat decreases blood pressure without increasing the heart rate, and inhibits tachycardia during the cold-pressor test, and (2) since only higher doses of ACE inhibitor may be capable of inducing vasodilation in the large arteries, despite having an identical hypotensive effect and the same degree of plasma ACE inhibition, the two different doses of perindoprilat induced different vascular effects. We propose that higher doses of perindoprilat may be necessary in order to inhibit vascular ACE, or to stimulate vasodilating systems.