[Antihypertensive effect of perindopril. Experimental pharmacology]

This review of the pharmacological effects of perindopril is based on data from the literature and divided into three parts: (i) demonstration of the antihypertensive effect of the drug; (ii) characterization of its inhibitory effect on the angiotensin-converting enzyme, (iii) understanding of its mechanisms of action. The antihypertensive effect of perindopril has been demonstrated in spontaneously hypertensive rats or in artificially induced renovascular hypertension (1 clip-2 kidney, 1 clip-1 kidney). The intensity and duration of this effect is dose-dependent and is increased by stimulation of the renin-angiotensin system (renovascular hypertension, sodium depletion). The peripheral vascular resistance is decreased without corresponding increase in heart rate. The drug-induced vasodilatation predominates in the kidney bed and is associated, in dogs on low water and salt diet, with a rise in natriuresis. These effects are accompanied by inhibition of the angiotensin-converting enzyme. In vitro peridoprilate (the main active diacid of perindopril) is a potent (Cl50: 1.5 to 3.2 nM) competitive and relatively specific inhibitor of the angiotensin-converting enzyme. In vitro, perindopril competitively inhibits the pressive response to angiotensin I. In rats given an oral dose of 1 mg.kg-1 the activity of plasma converting enzyme is inhibited for 24 hours and even longer if they are sodium-deplete. In spontaneously hypertensive rats, the antihypertensive effect of perindopril lasts longer than its inhibitory effect on the plasma converting enzyme. This dissociation suggests that the angiotensin-converting enzyme is inhibited in tissues, as has been shown in various tissues including rat kidney and aorta.(ABSTRACT TRUNCATED AT 250 WORDS)