Hypoxia increases superoxide anion production from bovine coronary microvessels, but not cardiac myocytes, via increased xanthine oxidase.

To determine if 30 min of hypoxia (PO2 8-10 Torr) affects basal, mitochondrial, or xanthine oxidase-derived lucigenin-detectable superoxide anion (O2.-) production by intact isolated bovine coronary microvessels and myocytes. O2.- was quantitated by lucigenin-elicited chemiluminescence. Antimycin A (10 microM) and hypoxanthine (0.1 mM) were employed to increase O2.- from mitochondria and xanthine oxidase, respectively. Chemiluminescence from microvessels and myocytes was enhanced (approximately twofold, P < 0.05, n = 8-10) by inhibition of Cu,Zn-SOD via pretreatment with diethyldithiocarbamate (10 mM, 30 min) and was decreased (P < 0.05, n = 8-10) by an intracellular scavenger of O2.- (10 mM Tiron), but not by added SOD (3 microM, n = 8-10). In the presence of SOD inhibition, hypoxia produced a hypoxanthine-dependent (n = 8-10) twofold increase in chemiluminescence (P < 0.05, n = 10) in microvessels but not in myocytes. Other combinations of hypoxia, antimycin, or hypoxanthine did not significantly alter chemiluminescence. Lucigenin appears to detect a basal intracellular source of O2.- in both microvessels and myocytes that is not derived from mitochondria or xanthine oxidase. Exposure to hypoxia does not appreciably increase basal O2.- in vessels or myocytes, but if exogenous hypoxanthine is supplied, microvessels show an increase in O2.- production presumably derived from xanthine oxidase.