Responses of blood pressure and angiotensin-converting enzyme activity to acute captopril administration in normotensive and hypertensive rats.
The purpose of these experiments ws to determine the dose of captopril which resulted in essentially complete blockade of tissue and plasma converting enzyme activity (CEA) and to correlate the effect of this dose of inhibitor on blood pressure and CEA in a number of normotensive and hypertensive rat models. Oral administration of captopril (0.3-10 mg/kg) induced a dose-related attenuation of CEA in plasma freshly drawn from normotensive conscious rats. After storage at -20 or 4 C before assay, both captopril-treated and untreated plasmas displayed markedly greater CEA. The converting enzyme inhibitor induced a parallel shift to the right of angiotensin I-induced blood pressure responses, reaching a 100-fold displacement of dose-dependent responses in the presence of 10 mg/kg captopril. Sixty minutes after oral administration of 10 mg/kg captopril, plasma CEA was blocked completely in all normo- and hypertensive models studied. This dose of the inhibitor reduced blood pressure in the sodium-deplete normotensive rat, the spontaneously hypertensive rat, and the initial phase two-kidney, one-clip Goldblatt rat but not in the sodium-replete normotensive rat, the spontaneously hypertensive rat, the mineralocorticoid hypertensive rat, or the chronic phase of two-kidney, one-clip Goldblatt rat. It is concluded that acute administration of captopril at a dose which results in complete blockade of plasma converting enzyme and severe attenuation of tissue converting enzyme reduces blood pressure in animals with high PRA but not in animals in which the PRA is low. (Endocrinology 108: 536, 1981)
D000803:Angiotensin I / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001800:Blood Specimen Collection; D002216:Captopril / Q000494:pharmacology*; D004039:Diet, Sodium-Restricted; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D012083:Renin / Q000097:blood
D000803:Angiotensin I; D011392:Proline; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D012083:Renin