Changes in NO bioavailabilty regulate cardiac O2 consumption:: control by intramitochondrial SOD2 and intracellular myoglobin

The aim of this study was to investigate the significance of two intracellular scavengers of nitric oxide ( NO): 1) superoxide dismutase ( SOD) ( SOD2) to scavenge intramitochondrial superoxide anion, and 2) cytosolic myoglobin ( Mb) in the regulation of tissue O-2 consumption. O-2 consumption was measured in vitro using a Clark- type O-2 electrode. SOD heterozygous mice ( SODHZ) ( n = 13) and SOD wildtype ( SODWT) ( n = 5) mice were used. Bradykinin ( BK, 10(-4) mol/ l) reduced O-2 consumption by 15% =/- 1 in hearts of SODHZ mice, which was significantly different from SODWT ( reduced by 24 +/- 0.4%). Tiron significantly increased the inhibition of O-2 consumption by BK in male mice from 15 +/- 1% ( n = 13) to 29 +/- 1.2% ( n = 4) at 10(-4) mol/ l concentration ( P < 0.05). The effect of carbachol was similar to BK. S- nitroso- N- acetyl penicillamine ( SNAP, 10(-4) mol/ l) reduced O-2 consumption by 39 +/- 1.3% in hearts of SODHZ mice, which was not significantly different from SODWT. But at 10(-7) mol/ l, SNAP caused significantly less inhibition of O-2 consumption in SODHZ mice. Mb knockout ( MbKO; Mb wild- type n = 6) and ( MbWT) mice ( n = 6) were also used. Kidney cortex was studied as the negative control because it does not contain Mb. BK ( 10(-4) mol/ l) reduced O-2 consumption by 32 +/- 2, 29 +/- 1, and 26 +/- 1% in the heart, skeletal muscle, and kidney of MbKO mice, which was also not significantly different from MbWT. SNAP ( 10(-4) mol/ l) reduced O-2 consumption by 39 +/- 3, 42 +/- 4, and 46 +/- 2% in the heart, skeletal muscle, and kidney of MbKO mice, which was also not significantly different from MbWT. N-G- nitro- L- arginine methyl ester ( P < 0.05) inhibited the reduction in O-2 consumption induced by BK in the MbKO mouse heart ( 15 +/- 1%), skeletal muscle ( 17 +/- 1%), and kidney ( 17 +/- 1%) as in the MbWT mice. These results suggest that the role of Mb as an intracellular NO scavenger is small, and the increase in mitochondrial superoxide in SODHZ mice may cause a decrease NO bioavailability and alter the control of myocardial O-2 consumption by NO.