Yonsei Med J.  1998 Jun;39(3):252-260. 10.3349/ymj.1998.39.3.252.

Mechanisms of relaxation of coronary artery by hypoxia

• Lee YH
• Kim JT
• Kang BS

• KMID: 711555
• DOI: http://doi.org/10.3349/ymj.1998.39.3.252

Abstract

This study was designed to clarify the dependency of hypoxic coronary vasodilation (HCD) on the endothelium and the role of the K+ channels on HCD in the rabbit coronary artery. HCD was investigated in an isolated left circumflex coronary artery precontracted with prostaglandin F2 alpha. Vascular rings were suspended for isometric tension recording in an organ chamber filled with Krebs-Henseleit (KH) solution. Hypoxia was induced by gassing the chamber with 95% N2 + 5% CO2 and was maintained for 15 approximately 25 min. Hypoxia elicited a vasodilation in the precontracted coronary artery with and without endothelium. There was no difference between the amplitude of the HCD induced by two consecutive hypoxic challenges and the effects of 20% O2 + 5% CO2 + 75% N2 and 95% O2 + 5% CO2 control K-H solution of subsequent responses to hypoxia. Inhibition of the cyclooxygenase pathway by treatment with indomethacin had no effect on HCD. Blockades of the tetraethylammonium chloride-sensitive K+ channel abolished HCD. Apamin, a blocker of the small conductance Ca(2+)-activated K+ (KCa) channel, and iberiotoxin, a blocker of the large conductance KCa channel had no effect on HCD, respectively. Glibenclamide, a blocker of the ATP-sensitive K+ (K+ATP) channel, reduced HCD. Cromakalim, an opener of the K+ATP channel, relaxed the coronary artery precontracted with prostaglandin F2 alpha. The degree of relaxation by cromakalim was similar to that by hypoxia while glibenclamide reduced both hypoxia- and cromakalim-induced vasodilatations. In conclusion, these results suggest that HCD is independent on endothelium and HCD is considered to be induced by activation of K+ATP channel.

Keyword

Hypoxic coronary vasodilatation; glibenclamide; K+ channel; K+ATP channel

MeSH Terms

Animal
Anoxia/physiopathology*
Coronary Vessels/physiopathology*
Coronary Vessels/drug effects
Cyclooxygenase Inhibitors/pharmacology
Enzyme Inhibitors/pharmacology
Female
Indomethacin/pharmacology
Male
Nitroarginine/pharmacology
Rabbits
Tetraethylammonium/pharmacology
Vasodilation/physiology*