Abstract
Several proline derivatives were synthesized and converting-enzyme inhibiting action of these compounds was evaluated by assessing the depressor action to angiotensin I-induced pressor re-sponses in anesthetized rats. Of all derivatives synthesized, D, L-2-methyl-3-mercaptopropanoyl-L-proline (D, L-m-m-p) was shown to have the most potent inhibiting action of converting-enzyme. Intra-venous administration of 0.1, 0.2 and 1.0 mg/kg of D, L-m-m-p showed 68%, 75%, and 80% suppression of the pressor action of angiotensin I, 0.15-0.6 μg/kg iv bolus. This inhibiting action was about ten times potent compared with Bradykinin Potentiator B indentified from snake venom of Agkistrodon halt's blomhoffii. Its converting-enzyme inhibiting action was effective in any routes of administration tested, i.e., intra-venous, subcutaneous and per Os. Effect on blood pressure of D, L-m-m-p (0.5 mg/kg, S.C.) was examined in rats having experi-mental models of renovascular hypertension. In one-kidney Goldblatt type rat, blood pressure reduction was observed in acute phase, but not observed in chronic phase. In two-kidney Goldblatt type rat, blood pressure reduction was observed in chronic phase. On the contrary, in normal rats no consistent blood pressure changes were observed. Thus, D, L-m-m-p is an active inhibitor of converting-enzyme by any routes of administration, it is a useful agent for investigation of renin-angiotensin system in animal experiment and also promising agent for diagnosis and treatment of renin dependent hypertension in human.
