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.
Systematic blood coagulation analyses were conducted in 32 severely hypertensive patients treated with the angiotensin converting enzyme inhibitor captopril. Two hours after the first captopril dose, fibrin monomer complexes had already increased. This rise was even more distinct after 26 h and 1 week. Tests after 6 and 12 months of therapy showed a regression of fibrin monomer complexes to pretreatment values. In several patients with a marked increase in fibrin monomer complexes, the partial thromboplastin time (PTT) became shorter and antiplasmin activity increased. The most pronounced increase in fibrin monomer complexes was seen in patients with a rapid and excessive blood pressure reduction. The concentration of fibrin monomer complexes also rose in 15 healthy normotensive subjects, after a single oral dose of captopril (25 mg). Additionally, the PTT was shortened and antiplasmin significantly rose. An inhibition of fibrinolysis by captopril could be demonstrated by the effect on fibrin plates and thrombus weight after streptokinase. Out of 58 patients with severe hypertension and atherosclerosis treated with captopril, 7 patients suffered vascular complications during antihypertensive therapy: myocardial infarction (n = 2), coronary insufficiency (1), cerebral ischemia (1), renal insufficiency (3). These ischemic lesions may be partly explained by the alterations of coagulation and fibrinolysis under captopril therapy.
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