NO ELICITS PROLONGED RELAXATION OF BOVINE PULMONARY-ARTERIES VIA ENDOGENOUS PEROXYNITRITE GENERATION

NO elicits prolonged relaxation of bovine pulmonary arteries via endog enous peroxynitrite generation. Am. J. Physiol. 273 (Lung Cell. Mol. P hysiol. 17): L437-L444, 1997.-We previously reported that acute exposu re of endothelium-removed bovine pulmonary arteries (BPA) to high leve ls (0.1 mM) of peroxynitrite (ONOO-) caused a prolonged guanosine 3',5 '-cyclic monophosphate-related relaxation that appeared to be mediated through a thiol-dependent generation of nitric oxide (NO). In this st udy, we examined the importance of endogenous ONOO- formation in the r egulation of BPA force generation by elevated physiological levels of NO. Exposure of BPA precontracted with 30 mM KCl to similar to 50 nM N O for 2 min caused a subsequent prolonged relaxation of KCl-induced fo rce and an increased release of NO (measured in head space gas after a 5-min deoxygenation with 95% N-2-5% CO2). This subsequent release of NO was reduced after depletion of tissue glutathione with diethyl male ate (DEM). Also, the NO-elicited prolonged relaxation of BPA was rever sed by post-NO treatment with 10 mu M methylene blue (MB; which inhibi ts guanylate cyclase stimulation by NO) or 1 mu M oxyhemoglobin (which traps NO). Furthermore, inhibiting the biosynthesis of endogenous sup eroxide anion (O-2(-) .) with 1 mu M diphenyliodonium (DPI) or scaveng ing O-2(-) . with 10 mM Tiron also promoted reversal of the NO-elicite d prolonged relaxation seen in BPA after NO gas exposure. During expos ure of BPA smooth muscle to similar to 50 nM NO gas, there appears to be a marked increase in ONOO- formation as detected by a DPI- and Tiro n-inhibitable prominent increase in luminol-dependent chemiluminescenc e and a decrease in O-2(-) . levels as detected by a reduction in luci genin-dependent chemiluminescence during exposure to NO. Thus, during exposure to elevated physiological levels of NO, BPA appear to produce ONOO-, a species that seems to participate in prolonging the initial relaxation to NO through a thiol-dependent trapping and/or regeneratio n of NO.