Related Experiment Video

Updated: May 10, 2026

Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine
10:05

Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine

Published on: July 7, 2016

Cardiac peroxisome proliferator-activated receptor δ (PPARδ) as a new target for increased contractility without

Zhih-Cherng Chen1, Kung Shing Lee, Li-Jen Chen

  • 1Department of Cardiology, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan.

Plos One
|June 1, 2013
PubMed
Abstract

Insights

Peroxisome proliferator-activated receptor delta (PPARδ) activation enhances cardiac contractility without altering heart rate. This suggests PPARδ is a potential therapeutic target for heart failure treatment, offering improved heart function without side effects on heart rate.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Pharmacology

Background:

  • Positive inotropic agents treat heart failure but affect heart rate.
  • Peroxisome proliferator-activated receptor delta (PPARδ) involvement in cardiac contraction is known, but its effect on heart rate is unclear.

Purpose of the Study:

  • To investigate the effect of PPARδ activation on heart rate using the agonist GW0742.
  • To determine if PPARδ can enhance cardiac contractility without affecting heart rate.

Main Methods:

  • Isolated hearts (Langendorff apparatus) and catheterized rats were used for in vitro and in vivo hemodynamic analysis.
  • Intracellular calcium levels and troponin I phosphorylation were measured using Western blotting.
  • The effects of GW0742 were assessed in normal and diabetic rats with heart failure, with and without the PPARδ blocker GSK0660.

Main Results:

  • GW0742 activated PPARδ, reversing cardiac contraction in diabetic rats with heart failure without changing heart rate.
  • In normal rats, GW0742 significantly enhanced cardiac contractility and dP/dtmax more than dobutamine, an effect blocked by GSK0660.
  • GW0742 increased intracellular calcium and troponin I phosphorylation, but did not alter heart rate, only mildly increasing blood pressure.

Conclusions:

  • PPARδ activation by GW0742 enhances cardiac contractility.
  • PPARδ activation does not affect heart rate.
  • PPARδ represents a promising therapeutic target for developing heart failure treatments with improved cardiac contractility and no heart rate side effects.

More Related Videos

Contractility Measurements on Isolated Papillary Muscles for the Investigation of Cardiac Inotropy in Mice06:22

Contractility Measurements on Isolated Papillary Muscles for the Investigation of Cardiac Inotropy in Mice

Published on: September 17, 2015

Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes07:32

Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes

Published on: May 25, 2022

Related Concept Videos

Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Pathophysiology of Cardiac Performance01:29

Pathophysiology of Cardiac Performance

Typical heart performance is influenced by heart rate, rhythm, myocardial contraction, and metabolism or blood flow. The cardiac muscle exhibits distinct electrophysiological features, including pacemaker activity and calcium channel control, which play a vital role in the heart's response to various drugs. The autonomic nervous system, comprising the sympathetic and parasympathetic branches, regulates heart rate. Sympathetic activation increases heart rate, while parasympathetic activation...
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
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...