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.

Related Concept Videos

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
Heart Failure II: Pathophysiology01:29

Heart Failure II: Pathophysiology

Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...