Related Experiment Video

Updated: Aug 31, 2025

Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System
08:01

Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System

Published on: June 11, 2020

8.2K

Angiotensin-(1-7) attenuates the negative inotropic response to acetylcholine in the heart

Carolina Nobre Ribeiro Pontes1, Sérgio Scalzo2, Itamar Couto Guedes Jesus2

  • 1Department of Physiological Sciences, Institute of Biological Sciences, Universidade Federal de Goiás, 74690-900 Goiânia, Brazil.

Peptides
|August 23, 2022
PubMed

Insights

Angiotensin-(1-7) [Ang-(1-7)] counter-regulates acetylcholine

Area of Science:

  • Cardiovascular Physiology
  • Autonomic Nervous System Regulation
  • Molecular Cardiology

Background:

  • Previous research indicates Angiotensin-(1-7) [Ang-(1-7)] influences cardiac function via the autonomic nervous system.
  • The specific impact of Ang-(1-7) on acetylcholine's (ACh) modulation of ventricular contractility remains unclear.
  • Investigating the intrinsic cardiac effects of Ang-(1-7) on cholinergic signaling is crucial for understanding cardiac regulation.

Purpose of the Study:

  • To determine if Ang-(1-7) modifies the magnitude of cardiac cholinergic effects.
  • To ascertain whether these modulatory effects are intrinsic to the heart.
  • To elucidate the receptor mechanisms involved in Ang-(1-7)'s action on cholinergic responses.

Main Methods:

  • Experiments conducted on anesthetized Wistar rats and isolated rat hearts.
  • Assessment of left ventricular end-systolic pressure (LVESP) and contractility indices (dP/dtmax, dP/dtmin).
  • Utilized Mas receptor antagonist (A-779) and adenylyl cyclase inhibitor (MDL-12,330A) to probe signaling pathways.
  • Isolated cardiomyocyte studies to evaluate effects on contraction and relaxation speeds.

Main Results:

  • Ang-(1-7) attenuated ACh-induced decreases in LVESP, dP/dtmax, and dP/dtmin in vivo and in isolated hearts.
  • Ang-(1-7) did not affect ACh's hypotensive action, suggesting specificity.
  • The observed effects were mediated via the Mas receptor, as they were blocked by A-779.
  • Adenylyl cyclase inhibition did not alter the Ang-(1-7) effects, ruling out that pathway.
  • In cardiomyocytes, Ang-(1-7) reduced ACh-induced decreases in contraction/relaxation speeds and shortening.

Conclusions:

  • Angiotensin-(1-7) [Ang-(1-7)] counter-regulates the myocardial contractile response to acetylcholine (ACh).
  • This regulation occurs via the Mas receptor and is independent of arterial pressure and heart rate.
  • These findings highlight an intrinsic cardiac mechanism by which Ang-(1-7) modulates cholinergic signaling.

Keywords:
AcetylcholineCardiac functionMas receptorRenin-Angiotensin System

More Related Videos

Measurement of Endothelium-Dependent Vasorelaxation in the Mouse Thoracic Aorta Using Tensometric Small Volume Chamber Myography09:47

Measurement of Endothelium-Dependent Vasorelaxation in the Mouse Thoracic Aorta Using Tensometric Small Volume Chamber Myography

Published on: August 12, 2022

3.3K
Impact of Intracardiac Neurons on Cardiac Electrophysiology and Arrhythmogenesis in an Ex Vivo Langendorff System06:40

Impact of Intracardiac Neurons on Cardiac Electrophysiology and Arrhythmogenesis in an Ex Vivo Langendorff System

Published on: May 22, 2018

10.8K

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...
493
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...
847
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...
891
Heart Failure Drugs: Inotropic Agents01:26

Heart Failure Drugs: Inotropic Agents

Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
699
Indirect-Acting Cholinergic Agonists: Pharmacological Actions01:30

Indirect-Acting Cholinergic Agonists: Pharmacological Actions

Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
756
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,...
585