Hyperkalemia exposure impairs EDHF-mediated endothelial function in the human coronary artery.
BACKGROUND
My colleagues and I have found in the porcine coronary artery that the pathway other than the nitric oxide (NG-nitro-L-arginine [L-NNA]-sensitive) and cyclooxygenase (indomethacin-sensitive) pathways of endothelium-dependent relaxation, related to the endothelium-derived hyperpolarizing factor (K+ channel-related), are altered after exposure to hyperkalemia. The present study was designed to examine whether this effect exists in the human coronary artery.


METHODS
Coronary artery rings obtained from explanted fresh human hearts were studied in organ chambers under physiologic pressure. The endothelium-dependent relaxation in response to calcium ionophore A23187 was studied in U46619 (30 nmol/L)-induced precontraction in the presence of the cyclooxygenase inhibitor indomethacin (7 mumol/L) and the nitric oxide biosynthesis inhibitor L-NNA (300 mumol/L). The effect of incubation with 20 mmol/L K+ for 1 hour on the relaxation was examined in other coronary rings.


RESULTS
In control rings, A23187 induced a maximal relaxation of 50.7% +/- 3.2% (n = 6). After 1 hour of exposure to 20 mmol/L K+, the relaxation was reduced to 30.4% +/- 4.6% (n = 6; p = 0.005). Incubation with hyperkalemia also significantly reduced the sensitivity (increased effective concentration that caused 50% of maximal relaxation) of the indomethacin- and L-NNA-resistant relaxation (-7.37 +/- 0.17 versus -8.28 +/- 0.27 log mol/L; p = 0.019).


CONCLUSIONS
Exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant, endothelium-dependent (endothelium-derived hyperpolarizing factor-related) relaxation in the human coronary artery. This suggests that the previously proposed mechanism of coronary dysfunction after exposure to cardioplegic and organ preservation solutions in animal vessels is also valid in the human heart.
He
G W
GW
Department of Surgery, University of Hong Kong, Grantham Hospital, Hong Kong. gwhe@hkucc.hku.hk
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001685:Biological Factors / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D006947:Hyperkalemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D001685:Biological Factors; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; C067410:endothelium-dependent hyperpolarization factor; D000001:Calcimycin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011188:Potassium; D007213:Indomethacin