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 pr eservation solutions) on endothelial function are contradictory. The e ndothelium-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 th e hypothesis that hyperkalemia may alter endothelial function through non-nitric oxide and noncyclooxygenase pathways Methods. Porcine coron ary artery rings (5 to 10 in each group) were studied in organ chamber s under physiologic pressure. After incubation with 20 or 50 mmol/L K for 1 hour, the response to substance P, an endothelium-dependent vas orelaxant peptide, in K+ (25 mmol/L)induced contraction was studied in the presence of the cyclooxygenase inhibitor indomethacin (7 mu mol/L ), the nitric oxide biosynthesis inhibitor N-G-nitro-L-arginine (L-NNA ) (300 mu mol/L), or the adenosine triphosphate-sensitive K+-channel b locker glybenclamide (3 mu mol/L) in comparison with control arteries (69.8 + 4.6% of K+ contraction). Results. Without exposure to hyperkal emia, indomethacin (with or without glybenclamide) did not alter but L -NNA significantly reduced the relaxation (39.7% +/- 3.7%, p < 0.001). After exposure to K+, the indomethacin- and L-NNA-resistant relaxatio n was further reduced (97.4% + 3.2% for 20 mmol/L K+, p < 0.0001; or 1 3.5% +/- 8.4% for 50 mmol/L K+, p < 0.05, compared with rings without exposure), whereas the indomethacin- and glybenclamide-resistant relax ation was not altered. Incubation with hyperkalemia (50 mmol/L) also s ignificantly reduced the sensitivity (increased EC(50)) of the indomet hacin- and L-NNA-resistant relaxation (-9.75 +/- 0.06 versus -9.33 +/- 0.04 log M, p < 0.01). Conclusions. Exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant, endothelium-dependent (endorhel ium-derived hyperpolarizing factor-related) relaxation. Our study may suggest a new mechanism of coronary dysfunction after exposure to hype rkalemia and open a new area for protection of coronary endothelium in cardiac surgery and for organ preservation in transplantation surgery .