Related Experiment Video

Updated: Jun 18, 2026

Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
07:21

Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice

Published on: September 28, 2015

Effects of combined angiotensin II and endothelin receptor blockade with developing heart failure: effects on left

R B New1, A C Sampson, M K King

  • 1Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.

Circulation
|September 20, 2000
PubMed
Abstract

Insights

Combined blockade of angiotensin II type 1 (AT(1)) and endothelin-1 (ET) receptors improved left ventricular (LV) function in a congestive heart failure (CHF) model. This approach offers a potential therapeutic strategy for CHF patients.

Area of Science:

  • Cardiovascular Physiology
  • Pharmacology
  • Heart Failure Research

Background:

  • Congestive heart failure (CHF) involves complex alterations in cardiac function and neurohormonal systems.
  • Angiotensin II type 1 (AT(1)) and endothelin-1 (ET) receptors play critical roles in cardiovascular regulation and pathophysiology of CHF.

Purpose of the Study:

  • To compare the effects of AT(1) receptor inhibition alone, ET receptor blockade alone, and combined blockade on left ventricular (LV) function in a CHF model.
  • To assess the impact of these interventions on myocardial contractility and neurohormonal activity.

Main Methods:

  • A porcine model of rapid atrial pacing-induced CHF was utilized.
  • Animals were randomized into five groups: rapid pacing, AT(1) blockade + pacing, ET blockade + pacing, combined blockade + pacing, and sham control.
  • Left ventricular function, stroke volume, peak wall stress, norepinephrine levels, and myocyte velocity of shortening were measured.

Main Results:

  • Combined AT(1) and ET receptor blockade significantly improved LV stroke volume compared to monotherapy or pacing alone.
  • ET receptor blockade, alone or in combination, reduced LV peak wall stress.
  • Combined blockade normalized elevated plasma norepinephrine levels and restored LV myocyte velocity of shortening to control levels.

Conclusions:

  • Combined AT(1) and ET receptor blockade effectively improved LV pump function in this CHF model.
  • Benefits are attributed to favorable effects on LV loading conditions, neurohormonal activity, and myocardial contractility.
  • Combined receptor blockade represents a promising therapeutic strategy for managing congestive heart failure.

More Related Videos

Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice09:40

Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice

Published on: May 13, 2019

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion08:35

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion

Published on: May 26, 2022

Related Concept Videos

Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers01:24

Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers

Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which indirectly block calcium...
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...
Mitral Regurgitation I: Introduction01:20

Mitral Regurgitation I: Introduction

Mitral regurgitation is characterized by the backward circulation of blood from the left ventricle to the left atrium during systole, a phase of the cardiac cycle when the heart contracts and pumps blood out of the chambers. This abnormal flow occurs primarily due to the dysfunction of the mitral valve or its supporting structures, which include the mitral leaflets, chordae tendineae, annulus, and papillary muscles.Etiology and Mechanisms:Primary Mitral Regurgitation: This type arises from...
Mitral Stenosis I: Introduction01:22

Mitral Stenosis I: Introduction

Mitral Valve Stenosis (MVS) is a heart condition where the mitral valve narrows, impeding blood circulation from the left atrium to the left ventricle. The etiology and pathophysiology of this condition are multifaceted, leading to a cascade of cardiovascular complications.Causes of Mitral Valve StenosisRheumatic Heart Disease: It is the main cause of mitral valve stenosis, particularly in developing nations. This condition arises from rheumatic fever, an inflammatory illness resulting from...
Myocarditis I: Introduction01:21

Myocarditis I: Introduction

Myocarditis is inflammation of the myocardium, which is the muscular layer of the heart.EtiologyMyocarditis has a diverse etiology, including a wide range of infectious and non-infectious causes:Infectious CausesViral: Common viruses include Coxsackie A and B, adenovirus, parvovirus B19, enteroviruses, and influenza A.Bacterial: Examples include infections caused by Streptococcus, Staphylococcus, and Mycoplasma species.Rickettsial: Infections like Rocky Mountain spotted fever can result in...
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...