PROPERTIES OF A SUPEROXIDE ANION-GENERATING MICROSOMAL NADH OXIDOREDUCTASE, A POTENTIAL PULMONARY-ARTERY P-O2 SENSOR

In this study, we describe properties of a microsomal NADH oxidoreduct ase that is a potential PO2-dependent source of vasoactive reactive O- 2 species in the calf pulmonary artery. Microsomes show an NADH-depend ent production of superoxide anion (O-2(-).), as detected by lucigenin -elicited chemiluminescence, a superoxide dismutase inhibited reductio n of nitro blue tetrazolium (NBT) and 2,6-dichlorophenol-indophenol, a nd O-2 consumption. The microsomal production of O-2(-). was modulated by physiologically relevant levels of NADH and PO2, and O-2(-). produ ction was reduced by inhibitors of NADH-dependent microsomal electron transport. Microsomes catalyzed an NADH-mediated reduction of several electron acceptor dyes, cytochrome c (rotenone insensitive) and methem oglobin. On reduction with dithionite, a cytochrome with an absorbance at similar to 558 nm was observed. Arterial O-2(-). levels (chemilumi nescence) were also reduced by NBT and microsomal electron transport i nhibitors. In pulmonary arteries, NET selectively inhibited PO2 and la ctate elicited changes in force generation, presumably by trapping O-2 (-). and preventing H2O2 formation. Thus these studies are consistent with an involvement of O-2(-).-derived H2O2 generation via a microsoma l NADH-cytochrome b(558) electron transport system in calf pulmonary a rtery smooth muscle PO2 and lactate-elicited tone responses.