Differing mechanisms of action of angiotensin-converting enzyme inhibition in black and white hypertensive patients. The Trandolapril Multicenter Study Group.
The antihypertensive effect of the angiotensin-converting enzyme inhibitor trandolapril administered in doses of 1, 2, and 4 mg/d was compared in 207 white patients and 91 black patients with mild to moderate hypertension following a double-blind, randomized, placebo-controlled, parallel study design. Trandolapril is a prodrug that is rapidly hydrolyzed to its active diacid metabolite, trandolaprilat. After 6 weeks of double-blind treatment, trandolapril lowered baseline sitting diastolic pressure in both white and black patients. A comparison of the antihypertensive 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 response (-6.5 mm Hg) was observed in the black patients at 4 mg/d. In contrast to the population differences in blood pressure, the decreases in angiotensin-converting enzyme activity were similar for both populations. 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. Therefore, it appears that the antihypertensive response of black patients is not completely explained by a reduction in angiotensin-converting enzyme activity. The lack of response at a lower dose but increasing response at a higher dose could reflect another vasodepressor activity of trandolapril or just be evidence of reduced sensitivity of high blood pressure in blacks to angiotensin-converting enzyme inhibition.
Weir
M R
MR
Clinical Research Unit, University of Maryland School of Medicine, Baltimore, USA.
Gray
J M
JM
Paster
R
R
Saunders
E
E
D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D044383:Black People; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007211:Indoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood; D044465:White People
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; C052035:trandolapril; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A; D012083:Renin; C061095:trandolaprilat