Depolarizing cardiac arrest and endothelium-derived hyperpolarizing factor-mediated hyperpolarization and relaxation in coronary arteries: the effect and mechanism.
OBJECTIVE
Depolarizing (hyperkalemic) solutions are widely used to preserve organs for transplantation and for cardiac operations. We previously observed that exposure to hyperkalemia reduced endothelium-dependent, noncyclooxygenase- and non-nitric oxide-mediated relaxation. This study was designed to examine the mechanism of this effect with regard to K channels and the associated membrane potential changes.


METHODS
Porcine coronary artery rings were studied in organ chambers. After incubation of the tissue with 20 or 50 mmol/L doses of potassium for 1 hour, the endothelium-derived hyperpolarizing factor-mediated relaxation in the artery and the membrane hyperpolarization in a single coronary smooth muscle cell were studied.


RESULTS
The endothelium-derived hyperpolarizing factor-mediated relaxation induced by substance P, which could be significantly inhibited by the Ca(2+)-activated K channel blocker tetraethylammonium but only to a lesser extent by the adenosine triphosphate-sensitive K channel blocker glibenclamide, was significantly reduced. Substance P-induced hyperpolarization of the membrane potential was also significantly reduced by the hyperkalemic incubation with a significantly elevated resting membrane potential.


CONCLUSIONS
Depolarizing arrest reduces endothelium-derived hyperpolarizing factor-mediated membrane hyperpolarization and relaxation by affecting mainly the Ca(2+)-activated K channels and by depolarizing the membrane for a prolonged period. We suggest that this is one of the mechanisms for coronary dysfunction after exposure to depolarizing (hyperkalemic) cardioplegic and organ-preservation solutions and that, therefore, "perfect" protection of the heart or other organs should restore the endothelium-derived hyperpolarizing factor-related endothelial function.
He
G W
GW
Department of Surgery, University of Hong Kong, Grantham Hospital, Hong Kong.
Yang
C Q
CQ
Yang
J A
JA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006324:Heart Arrest, Induced / Q000379:methods*; D006947:Hyperkalemia; D066298:In Vitro Techniques; D007213:Indomethacin; D008297:Male; D008564:Membrane Potentials; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D019188:Organ Preservation Solutions; D015221:Potassium Channels / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001685:Biological Factors; D019188:Organ Preservation Solutions; D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; C067410:endothelium-dependent hyperpolarization factor; D013373:Substance P; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007213:Indomethacin