Effects of a New Angiotensin-Converting Enzyme Inhibitor, MK 421, in Normal Men and Patients

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Effects of MK 421, a new angiotensin-converting enzyme inhibitor, were studied 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 Bartters syndrome, in the recumbent position. In all of them blood pressure (BP) fell, plasma angiotension 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. Then the effects attenuated gradually but still remained 24 h. In the same 5 normal men angiotension I (AI) was infused iv at a rate of 20 ng/kg Emin from 0900 h to 1500 h, from 2030 h to 2100 h, and the next morning from 0830 h 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. Then these inhibitory effects on the AI were attenuated but still remained at 24 h. The 2 patients with essential hypertension and patient with malignant hypertension were 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.
社団法人日本内分泌学会の論文

Effects of a New Angiotensin-Converting Enzyme Inhibitor, MK 421, in Normal Men and Patients

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