Changes in NO bioavailability 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 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. Bradykinin (BK, 10-4 mol/l) reduced O2 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 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 BK. S-nitroso-N-acetyl penicillamine (SNAP, 10-4 mol/l) reduced O2 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 O2 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 O2 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 O2 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. NG-nitro-l-arginine methyl ester (P < 0.05) inhibited the reduction in O2 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 O2 consumption by NO.
Li
Wei
W
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
Jue
Thomas
T
Edwards
John
J
Wang
Xipping
X
Hintze
Thomas H
TH
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D001920:Bradykinin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006579:Heterozygote; D007425:Intracellular Membranes / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010641:Phenotype; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D001920:Bradykinin; D002217:Carbachol; D004791:Enzyme Inhibitors; D009211:Myoglobin; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2