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

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

Biochemistry and Molecular Medicine

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

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 language	English (US)
Journal	American Journal of Physiology - Heart and Circulatory Physiology
Volume	286
Issue number	1 55-1
State	Published - Jan 2004

Keywords

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

ASJC Scopus subject areas

Physiology

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@article{5e2ade2a5bb34c4ea53b933c632dd63e,

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

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.",

keywords = "Bradykinin, Carbachol, Myoglobin knockout mouse, S-nitroso-N-acetyl penicillamine, Superoxide dismutase-2 heterozygous mouse, Tiron",

author = "Wei Li and Thomas Jue and John Edwards and Xipping Wang and Hintze, {Thomas H.}",

year = "2004",

month = jan,

language = "English (US)",

volume = "286",

journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",

issn = "1931-857X",

publisher = "American Physiological Society",

number = "1 55-1",

}

TY - JOUR

T1 - Changes in NO bioavailabilty regulate cardiac O2 consumption

T2 - Control by intramitochondrial SOD2 and intracellular myoglobin

AU - Li, Wei

AU - Jue, Thomas

AU - Edwards, John

AU - Wang, Xipping

AU - Hintze, Thomas H.

PY - 2004/1

Y1 - 2004/1

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.

KW - Bradykinin

KW - Carbachol

KW - Myoglobin knockout mouse

KW - S-nitroso-N-acetyl penicillamine

KW - Superoxide dismutase-2 heterozygous mouse

KW - Tiron

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M3 - Article

C2 - 12919935

AN - SCOPUS:0347747971

VL - 286

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 1 55-1