DIFFERING MECHANISMS OF ACTION OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN BLACK-AND-WHITE HYPERTENSIVE PATIENTS

The antihypertensive effect of the angiotensin-converting enzyme inhib itor trandolapril administered in doses of 1, 2, and 4 mg/d was compar ed in 207 white patients and 91 black patients with mild to moderate h ypertension following a double-blind, randomized, placebo-controlled, parallel study design. Trandolapril is a prodrug that is rapidly hydro lyzed to its active diacid metabolite, trandolaprilat. After 6 weeks o f double-blind treatment, trandolapril lowered baseline sitting diasto lic pressure in both white and black patients. A comparison of the ant ihypertensive response of the two populations revealed that the black patients required between two and four times the dose of trandolapril to obtain a response similar to that observed in the white patients. A dose of 1 mg/d trandolapril resulted in a 6.1 mm Hg mean decrease in baseline sitting diastolic pressure for white patients; a similar resp onse (-6.5 mm Hg) was observed in the black patients at 4 mg/d. In con trast to the population differences in blood pressure, the decreases i n angiotensin-converting enzyme activity were similar for both populat ions. An evaluation of trandolaprilat levels revealed that there were no racial differences in the trandolaprilat concentrations required to achieve a given degree of angiotensin-converting enzyme inhibition. T herefore, it appears that the antihypertensive response of black patie nts is not completely explained by a reduction in angiotensin-converti ng enzyme activity. The lack of response at a lower dose but increasin g response at a higher dose could reflect another vasodepressor activi ty of trandolapril or just be evidence of reduced sensitivity of high blood pressure in blacks to angiotensin-converting enzyme inhibition.