Related Experiment Video

Updated: Apr 4, 2026

Evaluation of Vascular Control Mechanisms Utilizing Video Microscopy of Isolated Resistance Arteries of Rats
10:28

Evaluation of Vascular Control Mechanisms Utilizing Video Microscopy of Isolated Resistance Arteries of Rats

Published on: December 5, 2017

9.9K

15-Hydroxyeicosatetraenoic Acid and GPR39 Together Orchestrate Coronary Autoregulation: A Comprehensive Metabolomic

D Elizabeth Le1,2, Masaki Kajimoto1, Yan Zhao1

  • 1Knight Cardiovascular Institute.

Biorxiv : the Preprint Server for Biology
|April 3, 2026
PubMed

Insights

The G protein-coupled receptor 39 (GPR39) and 15-hydroxyeicosatetraenoic acid (15-HETE) are key to maintaining constant coronary blood flow (CBF) during reduced coronary driving pressure (CDP). Blocking GPR39 abolishes this vital autoregulation.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Mechanisms of Autoregulation
  • G Protein-Coupled Receptors

Background:

  • Coronary autoregulation maintains constant coronary blood flow (CBF) despite changes in coronary driving pressure (CDP).
  • The precise molecular mechanisms underlying coronary autoregulation remain largely unknown.
  • This study investigates the role of G protein-coupled receptor 39 (GPR39) and its agonist 15-hydroxyeicosatetraenoic acid (15-HETE) in this process.

Purpose of the Study:

  • To elucidate the mechanism of coronary autoregulation.
  • To test the hypothesis that GPR39 and 15-HETE orchestrate coronary autoregulation.

Main Methods:

  • Coronary stenoses were created in dogs to measure CBF and CDP.
  • Blood samples were analyzed for various metabolites, including 15-HETE.
  • A specific GPR39 antagonist (VC108) was administered to assess its impact on hemodynamics and coronary autoregulation.

Main Results:

  • GPR39 was identified in coronary arterioles and heart tissue.
  • 15-HETE levels correlated with CDP within the autoregulatory range.
  • Administration of VC108 abolished coronary autoregulation, making CBF directly dependent on CDP and decreasing coronary microvascular resistance.

Conclusions:

  • GPR39 and 15-HETE play a crucial role in mediating coronary autoregulation when coronary driving pressure is reduced.
  • These findings reveal a novel mechanism for coronary autoregulation.
  • This discovery may inform future pharmacological treatments for coronary syndromes.
Abstract

Keywords:
15-HETECoronary autoregulationGPR39

More Related Videos

Mesenteric Artery Contraction and Relaxation Studies Using Automated Wire Myography07:51

Mesenteric Artery Contraction and Relaxation Studies Using Automated Wire Myography

Published on: September 22, 2011

29.7K
Surgical Placement of Catheters for Long-term Cardiovascular Exercise Testing in Swine12:37

Surgical Placement of Catheters for Long-term Cardiovascular Exercise Testing in Swine

Published on: February 9, 2016

14.0K

Related Concept Videos

Autoregulation of Blood Flow01:17

Autoregulation of Blood Flow

Autoregulation mechanisms are characterized by their inherent capacity for self-regulation without necessitating specific nervous stimulation or endocrine control. These mechanisms facilitate the adjustment of blood flow and, therefore, perfusion specific to each tissue region. This self-regulation encompasses chemical signals and myogenic controls.
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation....
9.1K
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...
7.0K
Regulation of the Cardiovascular System01:27

Regulation of the Cardiovascular System

The regulation of the cardiovascular system allows the body to adapt to various demands and maintain homeostasis.
The regulation of the cardiovascular system involves the autonomic nervous system (ANS), baroreceptors, and chemoreceptors, ensuring that heart rate and blood pressure are appropriately modulated in response to varying physiological demands.
The ANS comprises two main divisions: the sympathetic and parasympathetic nervous systems. The sympathetic nervous system enhances...
5.2K
Neural Regulation of Blood Pressure01:18

Neural Regulation of Blood Pressure

The neural regulation of blood pressure involves intricate interactions between the autonomic nervous system (ANS) and cardiovascular system, ensuring adequate perfusion of tissues. This regulation primarily occurs through baroreceptor and chemoreceptor reflexes, involving both short-term and long-term mechanisms.
Baroreceptor Reflex
Baroreceptors, located in the carotid sinuses and aortic arch, detect changes in blood pressure. When blood pressure rises, these stretch-sensitive receptors...
8.8K
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
6.8K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
8.3K