Related Experiment Video

Updated: Jul 28, 2025

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
08:15

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease

Published on: May 10, 2024

614

Renin-Angiotensin System Antagonism Protects the Diabetic Heart from Ischemia/Reperfusion Injury in Variable

Aisha Al-Kouh1, Fawzi Babiker1, Maie Al-Bader1

  • 1Department of Physiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Kuwait City 13110, Kuwait.

Pharmaceuticals (Basel, Switzerland)
|June 1, 2023
PubMed
Abstract

Insights

Blocking the renin-angiotensin system with ACE inhibitors or AT1R blockers protects diabetic hearts from injury. This treatment reduces inflammation and apoptosis, improving heart function and reducing infarct size.

Area of Science:

  • Cardiovascular Research
  • Endocrinology
  • Pharmacology

Background:

  • Diabetes mellitus (DM) is a significant risk factor for ischemic heart diseases (IHD).
  • The renin-angiotensin system (RAS) plays a role in cardiac function, but its protective mechanisms against ischemia-reperfusion (I/R) injury in diabetes are not fully understood.

Purpose of the Study:

  • To evaluate the cardioprotective efficacy of angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor (AT1R) blockers, individually and in combination, against I/R injury in diabetic rat hearts.

Main Methods:

  • Diabetic rat hearts (acute hyperglycemia or STZ-induced) were subjected to I/R injury and treated with Captopril (ACE inhibitor), Losartan (AT1R antagonist), or both.
  • Hemodynamics, infarct size (TTC staining), apoptosis markers, antioxidant enzymes, eNOS, GLUT-4, and cytokine levels were assessed.

Main Results:

  • Both Captopril and Losartan, alone or combined, effectively protected diabetic hearts from I/R injury.
  • Significant improvements were observed in hemodynamics, reduced infarct size, and modulated apoptosis markers.
  • Treatments reduced pro-inflammatory cytokines and increased glucose transporter type 4 (GLUT-4) protein levels.

Conclusions:

  • RAS blockade confers significant protection to the diabetic heart against I/R injury.
  • This cardioprotection involves pathways that upregulate GLUT-4, decrease apoptosis and inflammation, and increase anti-inflammatory cytokines.
  • The protective mechanism appears independent of ERK1/2 and eNOS signaling.
Keywords:
RAScaptoprildiabetes mellitushyperglycemiaischemia reperfusionlosartan

More Related Videos

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

3.3K
A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis08:21

A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis

Published on: October 26, 2020

4.9K

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...
471
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,...
716
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...
793
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...
710
Hormonal Regulation01:33

Hormonal Regulation

The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
33.4K
Antihypertensive Drugs: Action of β1 Blockers01:17

Antihypertensive Drugs: Action of β1 Blockers

β1-receptors are primarily located in the heart and kidneys. In cardiac myocytes, these receptors interact with neurotransmitters released by the sympathetic nervous system during heightened activity or danger. As a result, β1-receptors get activated, initiating a series of biochemical processes. Excessive activation of beta receptors due to chronic stress can abnormally increase heart rate and contractility, resulting in high blood pressure or hypertension. To counteract this,...
494