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

Effects of MK 421, 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 (Pl 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. Then the effects attenuated gradually but still remained at 24 h. In the same 5 normal men angiotensin I (AI) was infused iv at a rate of 20 ng/kg . min from 0900 h to 1500 h, from 2030 h 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 Pl AI and PRA began to increase. The maximum effects were observed at 4 or 6 h. Then 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 was treated with MK 421 at a daily doses of 5 to 40 mg for 2 to 6 months. They all showed a fall in BP and no side-effects were noted. From these results it is concluded that MK 421 is a strong and long-acting antihypertensive drug and its clinical application seems very useful for the treatment of hypertension.