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Published on: September 17, 2015
T-lymphocyte and plasma angiotensin-converting enzyme activity during enalapril and losartan administration in humans
V V Petrov1, R H Fagard, P J Lijnen
1Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, Faculty of Medicine, University of Leuven (K.U. Leuven), Leuven, Belgium.
Insights
Enalapril, an ACE inhibitor, increased angiotensin-converting enzyme activity in T lymphocytes but decreased it in plasma. Losartan, an ARB, had no effect on ACE activity in either plasma or T lymphocytes.
Area of Science:
- Cardiovascular Pharmacology
- Immunopharmacology
- Hypertension Research
Background:
- The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in blood pressure regulation.
- Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARBs) are key antihypertensive medications targeting the RAAS.
- The effects of these drugs on ACE activity within specific immune cells, like T lymphocytes, are not fully understood.
Purpose of the Study:
- To investigate the long-term impact of enalapril (an ACE inhibitor) and losartan (an ARB) on ACE activity.
- To compare ACE activity in both plasma and circulating T lymphocytes in patients with essential hypertension.
- To determine if enalapril or losartan differentially affect ACE activity in immune cells versus plasma.
Main Methods:
- Randomized, placebo-controlled, double-blind, crossover study involving nine patients with essential hypertension.
- Patients received placebo, enalapril (20 mg/day), or losartan (50 mg/day) for 6-week periods.
- ACE activity was measured in plasma and T lymphocytes by quantifying substrate degradation and dipeptide formation using spectrofluorometry.
Main Results:
- Enalapril significantly suppressed plasma ACE activity (p < 0.01).
- Conversely, enalapril significantly stimulated ACE activity in circulating T lymphocytes (p < 0.05).
- Losartan demonstrated no significant effect on ACE activity in either plasma or T lymphocytes.
Conclusions:
- Long-term treatment with the ACE inhibitor enalapril induces ACE activity in human T lymphocytes.
- This induction occurs despite suppression of plasma ACE activity.
- Angiotensin II receptor type 1 antagonism with losartan does not alter ACE activity in plasma or T lymphocytes.
Abstract:
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.
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