Hyperkalemia alters EDHF-mediated hyperpolarization and relaxation in coronary arteries.
Hyperkalemic solutions are widely used to preserve organs for transplantation and for cardiac surgery. The present study was designed to test the hypothesis that hyperkalemia may alter endothelial function through a non-nitric oxide (NO) pathway, since preliminary studies have shown that the NO pathway may not be affected. Porcine coronary artery rings were studied in organ chambers. After incubation with 20 or 50 mM K+ for 1 h, the indomethacin- and NG-nitro-L-arginine+ (L-NNA)-resistant relaxation induced by A23187 or bradykinin, which could be further inhibited by tetraethylammonium but not glibenclamide, was significantly reduced. Incubation with hyperkalemia also significantly increased the concentration eliciting 50% of the maximal response to A23187 and bradykinin. A23187-induced hyperpolarization of the membrane potential was significantly reduced by hyperkalemic incubation. However, 1-h incubation with hyperkalemia does not affect the endothelial Ca2+ concentration. We conclude that exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant endothelium-dependent relaxation and endothelium-dependent hyperpolarization. This reduction in the relaxation and hyperpolarization is related to the endothelium-derived hyperpolarizing factor by affecting its effect on the smooth muscle cell, probably through partially depolarizing the membrane, and the Ca2(+)- activated K+ channels rather than by affecting its biosynthesis and/or release in the endothelial cell. Our study may suggest a new mechanism for coronary dysfunction after exposure to hyperkalemic cardioplegia and organ preservation solutions.
He
G W
GW
Grantham Hospital, Department of Surgery, University of Hong Kong, Hong Kong. gwhe@hkucc.hku.hk
Yang
C Q
CQ
Graier
W F
WF
Yang
J A
JA
D000818:Animals; D001158:Arteries; D001685:Biological Factors / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004594:Electrophysiology; D005260:Female; D006947:Hyperkalemia / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials; D013552:Swine; D014664:Vasodilation
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D000001:Calcimycin; D001920:Bradykinin