Related Experiment Video

Updated: Sep 29, 2026

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion
08:35

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion

Published on: May 26, 2022

Angiotensin-converting enzyme inhibition and endothelin antagonism for endothelial dysfunction in heart failure:

Johann Bauersachs1, Daniela Fraccarollo, Andreas Schäfer

  • 1Medizinische Klinik der Julius-Maximilians-Universität, Würzburg, Germany. j.bauersachs@medizin.uni-wuerzburg.de

Journal of Cardiovascular Pharmacology
|September 28, 2002
PubMed

Insights

Combination therapy of ACE inhibition and endothelin A receptor antagonism effectively improved endothelial dysfunction in chronic heart failure (CHF) models. This dual approach showed greater efficacy than monotherapy in restoring vasoreactivity and reducing oxidative stress.

Area of Science:

  • Cardiovascular Pharmacology
  • Renal Physiology
  • Endothelial Function

Background:

  • Chronic heart failure (CHF) is associated with endothelial vasomotor dysfunction.
  • Angiotensin-converting enzyme (ACE) inhibition and endothelin A (ET A) receptor antagonism are therapeutic strategies for cardiovascular diseases.
  • The combined effects of these therapies on endothelial dysfunction in CHF require further investigation.

Purpose of the Study:

  • To compare the effects of ACE inhibition (trandolapril) and ET A receptor antagonism (LU 135252), alone and in combination, on endothelial vasomotor dysfunction in experimental CHF.
  • To assess the impact of these treatments on vasoreactivity and superoxide anion formation in aortic rings from rats with CHF.

Main Methods:

  • Experimental chronic heart failure (CHF) was induced in Wistar rats via myocardial infarction.
  • Rats were treated with placebo, LU 135252 (ET A receptor antagonist), trandolapril (ACE inhibitor), or a combination of both.
  • Vasoreactivity (acetylcholine-induced relaxation) and superoxide anion formation were measured in isolated aortic rings.

Main Results:

  • CHF induced significant endothelial dysfunction, characterized by impaired vasoreactivity and increased superoxide anion formation.
  • Both monotherapy with LU 135252 and trandolapril significantly improved acetylcholine-induced relaxation compared to placebo.
  • Combination therapy demonstrated superior efficacy, further improving vasoreactivity and reducing the pathological rightward shift in relaxation response, with no significant difference in infarct size across groups.

Conclusions:

  • Monotherapy with ACE inhibition or ET A receptor antagonism ameliorates endothelial dysfunction in experimental CHF.
  • Combination therapy provides enhanced benefits for endothelial function in CHF compared to monotherapy.
  • These findings suggest a potential therapeutic advantage of combining ACE inhibitors and ET A receptor antagonists for managing endothelial dysfunction in chronic heart failure.

Related Concept Videos

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...
Heart Failure V: Medical Management01:30

Heart Failure V: Medical Management

Medical Management of Acute Decompensated Heart Failure (ADHF)The primary goals of therapy for patients hospitalized with acute decompensated heart failure (ADHF) include:Relieving symptomsOptimizing volume statusSupporting oxygenation and ventilationMaintaining cardiac output (CO) and end-organ perfusionIdentifying and addressing the cause of ADHFPreventing complicationsProviding patient education on factors precipitating HF exacerbationPlanning for dischargeOngoing monitoring and assessment...
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...
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 Drugs: β-Blockers01:22

Heart Failure Drugs: β-Blockers

β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation, vasodilation, and...
Heart Failure Drugs: Diuretics01:22

Heart Failure Drugs: Diuretics

Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be...