HYPERKALEMIA ALTERS EDHF-MEDIATED HYPERPOLARIZATION AND RELAXATION INCORONARY-ARTERIES

Hyperkalemic solutions are widely used to preserve organs for transpla ntation and for cardiac surgery. The present study was designed to tes t the hypothesis that hyperkalemia may alter endothelial function thro ugh a non-nitric oxide (NO) pathway, since preliminary studies have sh own that the NO pathway may not be affected. Porcine coronary artery r ings were studied in organ chambers. After incubation with 20 or 50 mM K+ for 1 h, the indomethacin- and N-G-nitro-L-arginine (L-NNA)-resist ant relaxation induced by A23187 or bradykinin, which could be further inhibited by tetraethylammonium but not glibenclamide, was significan tly 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 potentia l tvas significantly reduced by hyperkalemic incubation. However, l-h incubation with hyperkalemia does not affect the endothelial Ca2+ conc entration. We conclude that exposure to hyperkalemia reduces the indom ethacin- and L-NNA-resistant endothelium-dependent relaxation and endo thelium-dependent hyperpolarization. This reduction in the relaxation and hyperpolarization is related to the endothelium-derived hyperpolar izing factor by affecting its effect on the smooth muscle cell, probab ly 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 cor onary dysfunction after exposure to hyperkalemic cardioplegia and orga n preservation solutions.