Release of Nitric Oxide and Endothelium-Derived Hyperpolarizing Factor (EDHF) in Porcine Coronary Arteries Exposed to Hyperkalemia: Effect of Nicorandil

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Although the detrimental effect of hyperkalemia on coronary endothelium has been reported, there is no direct evidence regarding the effect of hyperkalemic exposure on nitric oxide (NO) release from the coronary endothelium. In addition, it is unclear whether nicorandil, a KATP channel opener, used as hyperpolarizing cardioplegia or added in hyperkalemic cardioplegic solution may protect endothelial function during cardiac surgery. The present study was designed to clarify NO release and the function of endothelium-derived hyperpolarizing factor (EDHF) in coronary circulation with respect to the effect of hyperkalemia and nicorandil. Nitric oxide was measured by using a NO-specific electrode, and EDHF-mediated relaxation was investigated in a myograph. Substance P- and calcium ionophore A23187-induced NO release was compared in porcine left circumflex coronary arteries before and after 1-hour exposure to 20 mM potassium (K+) at 37 degrees C. In coronary microarteries (diameter 200 to 450 microm), precontracted with U46619, in the presence of indomethacin (7 microM), NG-nitro-L-arginine (300 microM), and oxyhemoglobin (20 microM), EDHF-mediated relaxation was induced by bradykinin (-10 to -6.5 log M) after incubation with Krebs (control) or 20 mM K+ with or without 10 microM nicorandil at 37 degrees C for 1 hour. Neither substance P (58.8 +/- 5.0 versus 66.2 +/- 7.2 nmol/L) nor A23187 (86.6 +/- 9.0 versus 82.4 +/- 9.2 nmol/L in control) induced NO release was altered by hyperkalemic exposure (p > 0.05). In contrast, EDHF-mediated relaxation was decreased from 84.2% +/- 3.8% to 42.3% +/- 6.0% (p < 0.001) that was partially restored by nicorandil (50.7% +/- 5.5%, p < 0.05). Exposure to potassium at 20 mM does not affect NO release but impairs EDHF-mediated relaxation in coronary arteries. Supplementation of nicorandil in hyperkalemic cardioplegia may provide a protective effect on EDHF-related endothelial function.