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1 Department of Physiology, New York Medical College, Valhalla, NY, USA
2 Biological Chemistry, University of California Davis, Davis, CA, USA
* To whom correspondence should be addressed. E-mail: Thomas_Hintze{at}NYMC.edu.
The aim of this study was to investigate the significance of two intracellular scavengers of NO: a) SOD (SOD2) to scavenge intramitochondrial superoxide anion, and; 2) cytosolic myoglobin (MB), in the regulation of tissue O2 consumption. O2 consumption was measured in vitro using a Clark-type O2 electrode. SOD heterozygous mice (SODHZ) (n=13) and SOD wild type (SODWT) (n=5) mice were used. BK (10-4mol/l) reduced O2 consumption by 15%±1 in heart of SODHZ mice, which was significantly different from SODWT (reduced by 24±0.4%). Tiron significantly increased the inhibition of O2 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 bradykinin. SNAP (10-4mol/l) reduced O2 consumption by 39±1.3% in heart of SODHZ mice, which was not significantly different from SODWT. But at 10-7mol/l, SNAP caused significantly less inhibition of O2 consumption in SODHZ mice. MB knockout (MBKO) (n=6) and MBWT mice (n=6) were also used. Kidney cortex (Kid) was studied as the negative control since it does not contain myoglobin. BK (10-4mol/l) reduced O2 consumption by 32±2, 29±1, 26± 1% in heart, Skeletal muscle (SkeM) and Kid of MBKO mice, which was also not significantly different from MBWT. SNAP (10-4mol/l) reduced O2 consumption by 39±3, 42±4, 46±2% in heart, SkeM and Kid of MBKO mice, which was also not significantly different from MBWT. L-NAME ( P<0.05) inhibited the reduction in O2 consumption induced by BK in MBKO mouse heart (15±1%), SkeM(17±1%) and KidC(17±1%) as in the MBWT mice. These results suggest that the role of MB as 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 oxygen consumption by NO.
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