title: Mechanism of blood pressure reduction by teprotide (SQ 20881) in rats.
abstract: The mechanism by which the angiotensin converting enzyme inhibitor, teprotide (SQ 20881), lowers blood pressure was assessed in anesthetized normotensive and spontaneously hypertensive (SHR) rats. Teprotide always was administered at a maximally effective dose of 1 mg/kg. In six normal Wistar rats, teprotide lowered blood pressure only after sodium depletion, an effect which was abolished by bilateral nephrectomy. Saralasin infusion (5 microgram/kg/min) into salt-depleted normal rats induced a blood pressure effect similar to that of teprotide. When administered in addition to saralasin infusion, teprotide did not reduce blood pressure further in normal rats or in SHR. When blood pressure of normal rats was raised by angiotensin II infusion (200 ng/kg/min), teprotide did not affect the induced blood pressure increase. In contrast, the pressure rise induced by angiotensin I infusion (230 ng/kg/min) was reversed by saralasin, but again concomitant administration of teprotide did not induce further blood pressure reduction. Thus, under the particular conditions of the present study, teprotide did not appear to exert its hypotensive effect by any mechanism other than inhibition of the renin-angiotensin system. Furthermore, given at a maximally effective dose to the rat, it produced no greater vasodepressor effect than did saralasin.
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003864:Depression, Chemical; D004347:Drug Interactions; D005260:Female; D006973:Hypertension / Q000503:physiopathology; D009392:Nephrectomy; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D012504:Saralasin / Q000494:pharmacology; D012965:Sodium Chloride / Q000172:deficiency; D013722:Teprotide / Q000494:pharmacology*
chemical_list: D009842:Oligopeptides; D000804:Angiotensin II; D012965:Sodium Chloride; D000803:Angiotensin I; D013722:Teprotide; D012504:Saralasin