Nicorandil, a K.sub.ATP Channel Opener, Attenuates Ischemia-Reperfusion Injury in Isolated Rat Lungs

Purpose Nicorandil is a hybrid between nitrates and K.sub.ATP channel opener activators. The aim of this study was to evaluate the nicorandil's effects on ischemia-reperfusion (IR) lung injury and examine the mechanism of its effects. Methods Isolated rat lungs were divided into 6 groups. In the sham group, the lungs were perfused and ventilated for 150 min. In the IR group, after perfusion and ventilation for 30 min, they were interrupted (ischemia) for 60 min, and then resumed for 60 min. In the nicorandil (N) + IR group, nicorandil 6 mg was added before ischemia (nicorandil concentration was 75 [micro]g ml.sup.-1). In the glibenclamide + N + IR group, the L-NAME (N.sub.[omega]-Nitro-l-arginine methyl ester) + N + IR group and ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) + N + IR group, glibenclamide 3 [micro]M, L-NAME 100 [micro]M, and ODQ 30 [micro]M were added 5 min before nicorandil administration, respectively. We measured the coefficient of filtration (Kfc) of the lungs, total pulmonary vascular resistance, and the wet-to-dry lung weight ratio (WW/DW ratio). Results Kfc was significantly increased after 60 min reperfusion compared with baseline in the IR group, but no change in the sham group. An increase in Kfc was inhibited in the N + IR group compared with the IR group (0.92 ± 0.28 vs. 2.82 ± 0.68 ml min.sup.-1 mmHg.sup.-1 100 g.sup.-1; P < 0.01). Also, nicorandil attenuated WW/DW ratio was compared with IR group (8.3 ± 0.41 vs. 10.9 ± 2.5; P < 0.05). Nicorandil's inhibitory effect was blocked by glibenclamide and ODQ (P < 0.01), but not by L-NAME. Conclusions Nicorandil attenuated IR injury in isolated rat lungs. This protective effect appears to involve its activation as K.sub.ATP channel opener as well as that of the sGC-cGMP pathway.