Indapamide inhibits endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

Fundam Clin Pharmacol. 1993;7(8):443-8. doi: 10.1111/j.1472-8206.1993.tb01040.x.

Abstract

Experiments were designed to determine whether or not indapamide, an antihypertensive agent with vasodilator properties, inhibits endothelium-dependent contractions. Rings of aortae with and without endothelium from spontaneously hypertensive rats (SHR) were suspended in conventional organ chambers for the measurement of isometric force. Acetylcholine and adenosine diphosphate-beta-S in the presence of a nitric oxide synthase inhibitor, caused endothelium-dependent contractions, which were inhibited by indapamide. The compound (10(-4) M) also slightly reduced the contractions of rings without endothelium evoked by U-46,619, which activates thromboxane-endoperoxide receptors. These results demonstrate that indapamide inhibits endothelium-dependent contractions in the SHR aorta, and suggest that the inhibition is due, at least in part, to the action of the drug on the hypertensive vascular smooth muscle.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Acetylcholine / pharmacology
  • Adenosine Diphosphate / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / physiology*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology*
  • Hypertension / drug therapy*
  • Hypertension / physiopathology*
  • In Vitro Techniques
  • Indapamide / pharmacology*
  • Kinetics
  • Muscle Contraction / drug effects*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Prostaglandin Endoperoxides, Synthetic / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Receptors, Thromboxane / drug effects
  • Receptors, Thromboxane / physiology
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane A2 / pharmacology

Substances

  • Prostaglandin Endoperoxides, Synthetic
  • Receptors, Thromboxane
  • Thromboxane A2
  • Adenosine Diphosphate
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Indapamide
  • Acetylcholine