Endothelium-dependent contractions to acetylcholine, ATP and the calcium ionophore A 23187 in aortas from spontaneously hypertensive and normotensive rats

Fundam Clin Pharmacol. 2004 Jun;18(3):321-6. doi: 10.1111/j.1472-8206.2004.00247.x.

Abstract

The present study was designed to determine whether or not an increase in endothelial intracellular concentration of calcium ([Ca2+]i) evokes endothelium-dependent contractions in the aorta from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Acetylcholine, adenosine triphosphate (ATP) and the calcium ionophore, A 23187, produced endothelium-dependent relaxations in isolated aortic rings of both WKY and SHR. These relaxations in response to the three agonists were significantly smaller in the SHR when compared with the WKY. Endothelium-dependent contractions to acetylcholine, ATP and A 23187 were observed only in the aorta isolated from the SHR. In the presence of NG-nitro-L-arginine, an NO synthase inhibitor, the endothelium-dependent contractions in response to acetylcholine, ATP and A 23187 were potentiated significantly in the aorta SHR and were unmasked in that of WKY. However, the contractions were still significantly greater in SHR than in WKY. These contractions were abolished by indomethacin and valeryl salicylate (two cyclo-oxygenase inhibitors) as well as by S 18886 (a TP-receptor antagonist), indicating that the endothelium-dependent contraction produced by the three agonists share the same characteristics. The results of the present study indicate that the release/generation of endothelium-derived contracting factor, requires an increase in endothelial [Ca2+]i.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology*
  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • Calcimycin / pharmacology*
  • Endothelium, Vascular / physiology*
  • In Vitro Techniques
  • Ionophores / pharmacology*
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroarginine / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Thromboxane / antagonists & inhibitors
  • Vasodilator Agents / pharmacology*

Substances

  • Ionophores
  • Receptors, Thromboxane
  • Vasodilator Agents
  • Nitroarginine
  • Calcimycin
  • Adenosine Triphosphate
  • Nitric Oxide Synthase
  • Acetylcholine