Involvement of endogenous endothelin-1 in exercise-induced redistribution of tissue blood flow: an endothelin receptor antagonist reduces the redistribution

Circulation. 2002 Oct 22;106(17):2188-93. doi: 10.1161/01.cir.0000038362.16740.a2.

Abstract

Background: Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide. Exercise results in a significant redistribution of tissue blood flow, which greatly increases blood flow in active muscles but decreases it in the splanchnic circulation. We reported that exercise causes an increase of ET-1 production in the internal organ and then hypothesized that ET-1 participates in the exercise-induced redistribution of tissue blood flow. We investigated the effects of acute endothelin-A (ETA)-receptor blockade on regional tissue blood flow during exercise in rats.

Methods and results: Regional blood flow in the kidney, spleen, stomach, intestine, and muscles was measured using the microsphere technique before and during treadmill running of 30 minutes duration at 30 m/min after pretreatment with either an ETA-receptor antagonist (TA-0201; 0.5 mg/kg) or vehicle in rats. Blood flow in the kidney, spleen, stomach, and intestine was decreased by exercise, but the magnitude of the decrease after pretreatment with TA-0201 was significantly smaller than that after pretreatment with vehicle. Furthermore, the increase in blood flow to active muscles induced by exercise was significantly smaller in rats pretreated with TA-0201 than those pretreated with vehicle.

Conclusions: The present study revealed that ET-1-mediated vasoconstriction participates in the decrease of blood flow in the internal organs of rats during exercise, and therefore, that these actions of endogenous ET-1 partly contribute to the increase of blood flow in active muscles during exercise. The data suggest that endogenous ET-1 participates in the exercise-induced redistribution of tissue blood flow.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Circulation*
  • Digestive System / blood supply
  • Endothelin Receptor Antagonists*
  • Endothelin-1 / physiology*
  • Hemodynamics / drug effects
  • Indans / pharmacology
  • Lactic Acid / blood
  • Male
  • Muscle, Skeletal / blood supply
  • Physical Conditioning, Animal*
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Endothelin A
  • Regional Blood Flow / drug effects
  • Renal Circulation
  • Splanchnic Circulation
  • Sulfonamides / pharmacology

Substances

  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Indans
  • Pyrimidines
  • Receptor, Endothelin A
  • Sulfonamides
  • T 0201
  • 1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-
  • Lactic Acid