Reflex-hemodynamic adjustments and baroreflex sensitivity during converting enzyme inhibition with MK-421 in normal humans.

Invasive hemodynamic measurements and determination of baroreflex sensitivity were carried out in 12 mildly sodium-depleted normotensive volunteers in a randomized double-blind crossover study with a single dose of converting enzyme inhibitor, MK-421, and placebo. In supine humans at rest, MK-421 caused a reduction in blood pressure through a fall in total peripheral resistance and an increase in arterial compliance. Thus, MK-421 appears to dilate both resistance vessels and larger arteries. Cardiac output increased, but contrary to the effects of other vasodilators, the increase was due to a higher stroke volume with an unchanged heart rate. The lack of heart rate response may well reflect enhanced central parasympathetic cardiac inhibition. Head-up tilt on MK421 caused an additional decrease in blood pressure in 65% of the subjects. The major determinant for the blood pressure fall during tilt and converting enzyme inhibition was a decrease in cardiac performance, while the reflex increase of arteriolar and venous tone was largely unimpaired. The decreased stroke volume may be secondary to elimination of a positive inotropic effect of angiotensin II (All). It is also conceivable that in the absence of AH the inotropic response to sympathetic activation is inadequate during tilt in these sodium-depleted normotensive individuals. Baroreflex sensitivity to blood pressure increase (i.v. phenylephrine) was enhanced after MK 421. Arterial compliance was increased, and this may explain the altered baroreceptor sensitivity. However, a possible central nervous enhancement of baroreceptor sensitivity after MK-421 could not be ruled out in this study. (Hypertension 5 (supp I): 1-184—1-191, 1983)