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

Wei Li, Thomas Jue, John Edwards, Xipping Wang, Thomas H. Hintze

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Abstract

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. O 2 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 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 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. N G-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume286
Issue number1 55-1
StatePublished - Jan 2004

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Myoglobin
Nitric Oxide
Superoxide Dismutase
Skeletal Muscle
Kidney
Superoxides
Myocardium
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
Kidney Cortex
Penicillamine
NG-Nitroarginine Methyl Ester
Carbachol
Bradykinin

Keywords

  • Bradykinin
  • Carbachol
  • Myoglobin knockout mouse
  • S-nitroso-N-acetyl penicillamine
  • Superoxide dismutase-2 heterozygous mouse
  • Tiron

ASJC Scopus subject areas

  • Physiology

Cite this

Changes in NO bioavailabilty regulate cardiac O2 consumption : Control by intramitochondrial SOD2 and intracellular myoglobin. / Li, Wei; Jue, Thomas; Edwards, John; Wang, Xipping; Hintze, Thomas H.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 286, No. 1 55-1, 01.2004.

Research output: Contribution to journalArticle

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AU - Wang, Xipping

AU - Hintze, Thomas H.

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N2 - 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. O 2 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 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 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. N G-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.

AB - 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. O 2 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 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 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. N G-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.

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KW - Superoxide dismutase-2 heterozygous mouse

KW - Tiron

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