Potential role of NADH oxidoreductase-derived reactive O2 species in calf pulmonary arterial PO2-elicited responses.
Our laboratory has previously reported evidence that tone responses of isolated endothelium-removed calf pulmonary arteries elicited by changes in PO2 appear to be mediated via changes in H2O2 and guanosine 3',5'-cyclic monophosphate, and that the PO2 sensor mechanism is hypothesized to involve changes in superoxide anion (O2-.) production by a microsomal NADH-oxidoreductase, which is the major source of O2-. detected by lucigenin-elicited chemiluminescence (CL) in this tissue. In this study we examined if the flavoprotein-directed inhibitor of O2-. producing NAD(P)H oxidoreductases, diphenyliodonium (DPI), could be employed as an inhibitor of O2-. production by NADH oxidoreductase, which functions as a selective probe for PO2-elicited tone responses in calf pulmonary arterial smooth muscle. It was found that 1 microM DPI inhibited NADH-dependent production of CL in the arterial smooth muscle homogenate by 49% (n = 10). DPI reduced basal CL from endothelium-removed pulmonary arteries by 41% (n = 15). In endothelium-removed pulmonary arteries precontracted with U-46619, the hypoxic contraction of 2.3 +/- 0.5 g was reduced to 0.1 +/- 0.4 g (n = 7) by DPI, and the reoxygenation relaxation of 32.7 +/- 7.5% was decreased to 4.4 +/- 1.4% (n = 7). DPI did not have any significant effect on U-46619- or K(+)-elicited tone generation. DPI also did not alter the relaxation to H2O2 (1 microM-0.1 mM, n = 6), nitric oxide (0.42 nM-420 nM, n = 12), or isoproterenol (1 nM-1 microM, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002417:Cattle; D005420:Flavoproteins / Q000378:metabolism; D006652:Histological Techniques; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009130:Muscle, Smooth / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010313:Partial Pressure; D011651:Pulmonary Artery / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D001713:Biphenyl Compounds; D005420:Flavoproteins; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D009243:NAD; C031291:diphenyliodonium; D010088:Oxidoreductases; D010100:Oxygen