T-lymphocyte and plasma angiotensin-converting enzyme activity during enalapril and losartan administration in humans.
This study evaluated the long-term effects of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II type 1 receptor antagonist losartan on the angiotensin-converting enzyme activity in T lymphocytes and plasma in patients with essential hypertension. The study was a randomized, placebo-controlled, double-blind, crossover design. Nine patients with sitting blood pressure > or = 95 mm Hg and < or = 105 mm Hg at the end of a 4-week placebo run-in period entered the double-blind phase of the study, which consisted of three 6-week periods during which patients were treated with placebo, enalapril (20 mg, once daily), or losartan (50 mg, once daily) The angiotensin-converting enzyme activity in T lymphocytes was measured as the activity of the degradation of the substrate Hippuryl-His-Leu and as the appearance of the dipeptide His-Leu, which was quantified spectrofluorometrically. Enalapril but not losartan suppressed (p < or = 0.01) the angiotensin-converting enzyme activity in plasma, whereas it stimulated (p < or = 0.05) the angiotensin-converting enzyme activity in circulating T lymphocytes. Our data document induction of angiotensin-converting enzyme in human T lymphocytes during long-term treatment with the angiotensin-converting enzyme inhibitor enalapril. Angiotensin II receptor type 1 antagonism with losartan had no effect on plasma or lymphocytic angiotensin-converting enzyme.
Petrov
V V
VV
Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, Faculty of Medicine, University of Leuven (K.U. Leuven), Leuven, Belgium.
Fagard
R H
RH
Lijnen
P J
PJ
D000284:Administration, Oral; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D018709:Statistics, Nonparametric; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000201:enzymology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D019808:Losartan