Effects of a new angiotensin-converting enzyme inhibitor, MK 421, in normal men and patients.

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Abstract
Effects of MK 421 [N-[(s)-1(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline], a new angiotensin-converting enzyme inhibitor, were studied in normal men and patients. MK 421 was given at 0900 h as a single oral dose of 20 mg, to 5 normal men and 2 patients with essential hypertension and 10 mg to a patient with Bartter''s syndrome, in the recumbent position. In all of them blood pressure (BP) fell, plasma angiotensin I (P1 AI) and plasma renin activity (PRA) increased, and plasma aldosterone (PA) decreased from 2 h to 6 h. Maximum effects were observed at 4 or 6 h. The effects attenuated gradually but still remained at 24 h. In the same 5 normal men angiotensin I (AI) was infused i.v. at a rate of 20 ng/kg .cntdot. min from 0900 to 1500 h, from 2030 to 2100 h, and the next morning from 0830 to 0900 h. At first the BP rose and PA increased. The onset of the BP fall was at 35, 55, 60, 70 and 85 min in each subject, respectively. Then the BP and PA began to decrease and the P1 AI and PRA began to increase. The maximum effects were observed at 4 or 6 h. These inhibitory effects on the AI were attenuated but still remained at 24 h. The 2 patients with essential hypertension and a patient with malignant hypertension were treated with MK 421 daily doses of 5-40 mg for 2-6 mo. They all showed a fall in BP and no side effects were noted. MK 421 is a strong and long-acting antihypertensive drug and its clinical application seems very useful for the treatment of hypertension.