[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)
Barthelmebs
M
M
Institut de pharmacologie et de médecine expérimentale, URA DO589 CNRS, Strasbourg, France.
Devissaguet
M
M
Imbs
J L
JL
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy*; D006978:Hypertension, Renovascular / Q000188:drug therapy; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D013564:Sympathetic Nervous System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril
Effet antihypertenseur du perindopril. Pharmacologie expérimentale.