Hyperkalemia alters endothelium-dependent relaxation through non-nitric oxide and noncyclooxygenase pathway: a mechanism for coronary dysfunction due to cardioplegia.

Background. Reported results of hyperkalemia (cardioplegia or organ preservation solutions) on endothelial function are contradictory. The endothelium-dependent relaxation is related to three major mechanisms: cyclooxygenase, nitric oxide, and endothelium-derived hyperpolarizing factor (K + channel related). The present study was designed to test the hypothesis that hyperkalemia may alter endothelial function through non—nitric oxide and noncyclooxygenase pathways. Methods. Porcine coronary artery rings (5 to 10 in each group) were studied in organ chambers under physiologic pressure. After incubation with 20 or 50 mmol/L K + for 1 hour, the response to substance P, an endothelium-dependent vasorelaxant peptide, in K + (25 mmol/L)-induced contraction was studied in the presence of the cyclooxygenase inhibitor indomethacin (7 μmol/L), the nitric oxide biosynthesis inhibitor N G -nitro-l-arginine (L-NNA) (300 μmol/L), or the adenosine triphosphate—sensitive K + -channel blocker glybenclamide (3 μmol/L) in comparison with control arteries (69.8 ± 4.6% of K + contraction). Results. Without exposure to hyperkalemia, indomethacin (with or without glybenclamide) did not alter but L-NNA significantly reduced the relaxation (39.7% ± 3.7%, p + , the indomethacin- and L-NNA-resistant relaxation was further reduced (7.4% ± 3.2% for 20 mmol/L K + , p + , p 50 ) of the indomethacin- and L-NNA-resistant relaxation (−9.75 ± 0.06 versus −9.33 ± 0.04 log M, p Conclusions. Exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant, endothelium-dependent (endothelium-derived hyperpolarizing factor-related) relaxation. Our study may suggest a new mechanism of coronary dysfunction after exposure to hyperkalemia and open a new area for protection of coronary endothelium in cardiac surgery and for organ preservation in transplantation surgery.