Lys-[Leu8,des-Arg9]-bradykinin blocks lipopolysaccharide-induced SHR aorta hyperpolarization by inhibition of Ca(++)- and ATP-dependent K+ channels

Eur J Pharmacol. 2004 Sep 13;498(1-3):163-9. doi: 10.1016/j.ejphar.2004.07.002.

Abstract

The mediators involved in the hyperpolarizing effects of lipopolysaccharide and of the bradykinin B1 receptor agonist des-Arg9-bradykinin on the rat aorta were investigated by comparing the responses of aortic rings of spontaneously hypertensive and normotensive Wistar rats. Endothelized rings from hypertensive rats were hyperpolarized by des-Arg9-bradykinin and lipopolysaccharide, whereas de-endothelized rings responded to lipopolysaccharide but not to des-Arg9-bradykinin. In endothelized preparations, the responses to des-Arg9-bradykinin were inhibited by Nomega-nitro-L-arginine and iberiotoxin. De-endothelized ring responses to lipopolysaccharide were inhibited by iberiotoxin, glibenclamide and B1 antagonist Lys-[Leu8,des-Arg9]-bradykinin. This antagonist also inhibited hyperpolarization by des-Arg9-bradykinin and by the á2-adrenoceptor agonist, brimonidine. Our results indicate that Ca(2+)-sensitive K+ channels are the final mediators of the responses to des-Arg9-bradykinin, whereas both Ca(2+)- and ATP-sensitive K+ channels mediate the responses to lipopolysaccharide. The inhibitory effects of Lys-[Leu8,des-Arg9]-bradykinin is due to a direct action on Ca(2+)- and ATP-sensitive potassium channels.

Publication types

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

MeSH terms

  • Acetylcholine / pharmacology
  • Adenosine Triphosphate / physiology
  • Animals
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / physiology
  • Bradykinin / analogs & derivatives*
  • Bradykinin / pharmacology
  • Brimonidine Tartrate
  • Cromakalim / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / physiology
  • In Vitro Techniques
  • Kallidin / analogs & derivatives*
  • Kallidin / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Male
  • Membrane Potentials / drug effects
  • Peptides / pharmacology
  • Potassium Channels, Calcium-Activated / antagonists & inhibitors*
  • Potassium Channels, Calcium-Activated / physiology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar
  • Vasodilator Agents / pharmacology

Substances

  • Lipopolysaccharides
  • Peptides
  • Potassium Channels, Calcium-Activated
  • Quinoxalines
  • Vasodilator Agents
  • bradykinin, Lys-Leu(8)-desArg(9)-
  • Cromakalim
  • bradykinin, des-Arg(9)-
  • Kallidin
  • Brimonidine Tartrate
  • iberiotoxin
  • Adenosine Triphosphate
  • Acetylcholine
  • Bradykinin