EDRF DOES NOT MEDIATE CORONARY VASODILATION SECONDARY TO SIMULATED ISCHEMIA - A STUDY ON K-ATP CHANNELS AND N-OMEGA-NITRO-L-ARGININE ON CORONARY PERFUSION-PRESSURE IN ISOLATED LANGENDORFF-PERFUSED GUINEA-PIG HEARTS

Several authors have alluded to the possible involvement of EDRF (NO) in ischemia-induced coronary artery dilation. Alternatively, it has be en suggested that opening of ATP-dependent K channels could play a key role in this context. We studied the effects of sulfonylureas and N-G -nitro-L-arginine (LNNA), a specific inhibitor of endothelial NO (EDRF ) synthesis, on ischemia-induced coronary vasodilation in isolated Lan gendorff-perfused guinea pig hearts arrested with 15 mM KCl in normal Tyrode, and isolated pig coronary arteries precontracted with 43 mM KC l. In Isolated Langerdorff-perfused guinea pig heart, when hypoxia was simulated by switching 100% O-2 in the perfusate to 100% N-2, coronar y perfusion pressure (CPP) fell from 90 cm H2O by 45 +/- 5 cm H2O. In the presence of LNNA, a specific inhibitor of NO synthetase in endothe lial cells, CPP dropped by 44 +/- 6 cm H2O (n = 6; +/- SEM, no statist ically significant). On biochemical simulation of ischemia (addition o f iodoacetate [IAA]), CPP dropped 40 +/- 6 cm H2O, and in experiments performed under the same conditions but in the presence of LNNA, CPP d ropped by 38 +/- 5 cm H2O (n = 6; +/- SEM; not statistically significa nt). When ischemia was simulated metabolically by equimolar replacemen t of 10 mM glucose with 2-deoxyglucose (DOG), an inhibitor of glycolys is CPP decreased by 24 +/- 1 cm H2O (n = 6; +/- SEM) after 15 minutes. This fall in CPP was almost prevented by 20 mu M glibenclamide, where as in the presence of 20 mu M LNNA the DOG-induced decrease in CPP was not significantly inhibited, and CPP decreased by 22 +/- 2.6 cm H2O ( n = 6; +/- SEM). In isolated pig coronary artery rings, maximal tensio n, achieved by depolarizing the smooth muscle cells by 43 mM KCl, decr eased by 37 +/- 7% upon simulated hypoxia by replacing 100% O-2 with 1 00% Na in the perfusate (n = 6; +/- SEM) in arteries with intact endot helium. In arteries without endothelium, maximal tension also dropped by 35 +/- 6% (not statistically significant). In the same experiments the decrease in tension could be largerly inhibited in the presence of 50 mu M glibenclamide. Our results clearly show that in isolated perf used guinea pig hearts, as well as in isolated pig coronary arteries, EDRF does not play a decisive role in the coronary dilatory response t o hypoxia and ischemia.