Key result
Single-dose MK421 boosts plasma renin activity ~3-fold without altering blood pressure.
Why the study?
The acute effects of MK421, a new angiotensin converting enzyme inhibitor, in humans were not previously characterized.
Answers are grounded in this paper and cite their sources.
No BP effect in normotensives cautions against low-dose assumptions; leaves optimal ACEI dosing and hypertensive efficacy open.
KASAI, Y., ABE, K., YASUJIMA, M., TAJIMA, J., SEINO, M., CHIBA, S., SATO, K., GOTO, T., OMATA, K., TANNO, M. and YOSHINAGA, K. Acute Effects of MK421, a New Angiotensin Converting Enzyme Inhibitor, in Man. Tohoku J. exp. Med., 1983, 141 (4), 417-422 Acute effects of MK421 were examined in 11 male normal volunteers. Oral administration of 5mg of MK421 did not induce any changes in blood pressure or pulse rate. Plasma renin activity increased significantly from 7.3±2.9ng/ml to 22.2±7.1 (p<0.05), whereas plasma aldosterone concentration did not change. Blood kinin, or urinary excretion of kallikrein and of prostaglandin E did not chage. However, urinary excretion of sodium increased significantly from 44.0±6.8mEq/4 hr to 56.5±6.5 (p<0.02) following the administration of MK421. The present results show that an increased renin release induced by MK421 is independent of change in blood pressure, and also suggest that MK421 may have a direct action on the renal tubules.
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Kasai et al. (1983) studied Healthy volunteers (n=11). MK421 vs. Baseline was evaluated on Plasma renin activity (ng/ml) (p=<0.05). A single 5 mg oral dose of MK421 significantly increased plasma renin activity and urinary sodium excretion in normal male volunteers without altering blood pressure.
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