Hypoxia-augmented constriction of deep femoral artery mediated by inhibition of eNOS in smooth muscle

Jung A. Han, Eun Yeoung Seo, Hae Jin Kim, Su Jung Park, Hae Young Yoo, Jin Young Kim, Dong Min Shin, Jin Kyoung Kim, Yin Hua Zhang, Sung Joon Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

In contrast to the conventional belief that systemic arteries dilate under hypoxia, we found that α-adrenergic contraction of rat deep femoral artery (DFA) is largely augmented by hypoxia (HVCDFA) while hypoxia (3% PO2) alone had no effect. HVCDFA was consistently observed in both endothelium-intact and -denuded vessels with partial pretone by phenylephrine (PhE) or by other conditions (e.g., K+channel blocker). Patch-clamp study showed no change in the membrane conductance of DFA myocytes by hypoxia. The RhoA-kinase inhibitor Y27632 attenuated HVCDFA. The nitric oxide synthase inhibitor [nitro-L-arginine methyl ester (L-NAME)] and soluble guanylate cyclase inhibitor [oxadiazole quinoxalin (ODQ)] strongly augmented the PhE-pretone, while neither of the agents had effect without pretone. NADPH oxidase type 4 (NOX4) inhibitors (diphenylene iodonium and plumbagin) also potentiated PhE-pretone, which was reversed by NO donor. No additive HVCDFA was observed under the pretreatment with L-NAME, ODQ, or plumbagin. Western blot and immunohistochemistry analysis showed that both NOX4 and endothelial nitric oxide synthase (eNOS) are expressed in smooth muscle layer of DFA. Various mitochondria inhibitors (rotenone, myxothiazol, and cyanide) prevented HVCDFA. From the pharmacological data, as a mechanism for HVCDFA, we suggest hypoxic inhibition of eNOS in myocytes. The putative role of NOX4 and mitochondria requires further investigation. The HVCDFA may prevent imbalance between cardiac output and skeletal blood flow under emergent hypoxia combined with increased sympathetic tone.

Original languageEnglish
Pages (from-to)C78-C88
JournalAmerican Journal of Physiology - Cell Physiology
Volume304
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1

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Nitric Oxide Synthase Type III
Femoral Artery
Constriction
Smooth Muscle
NADPH Oxidase
Phenylephrine
Oxadiazoles
Quinoxalines
NG-Nitroarginine Methyl Ester
Muscle Cells
Mitochondria
Rotenone
Cyanides
Nitric Oxide Synthase
Cardiac Output
Adrenergic Agents
Endothelium
Phosphotransferases
Arteries
Western Blotting

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

Han, Jung A. ; Seo, Eun Yeoung ; Kim, Hae Jin ; Park, Su Jung ; Yoo, Hae Young ; Kim, Jin Young ; Shin, Dong Min ; Kim, Jin Kyoung ; Zhang, Yin Hua ; Kim, Sung Joon. / Hypoxia-augmented constriction of deep femoral artery mediated by inhibition of eNOS in smooth muscle. In: American Journal of Physiology - Cell Physiology. 2013 ; Vol. 304, No. 1. pp. C78-C88.
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Hypoxia-augmented constriction of deep femoral artery mediated by inhibition of eNOS in smooth muscle. / Han, Jung A.; Seo, Eun Yeoung; Kim, Hae Jin; Park, Su Jung; Yoo, Hae Young; Kim, Jin Young; Shin, Dong Min; Kim, Jin Kyoung; Zhang, Yin Hua; Kim, Sung Joon.

In: American Journal of Physiology - Cell Physiology, Vol. 304, No. 1, 01.01.2013, p. C78-C88.

Research output: Contribution to journalArticle

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AU - Seo, Eun Yeoung

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AU - Kim, Jin Young

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AU - Zhang, Yin Hua

AU - Kim, Sung Joon

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N2 - In contrast to the conventional belief that systemic arteries dilate under hypoxia, we found that α-adrenergic contraction of rat deep femoral artery (DFA) is largely augmented by hypoxia (HVCDFA) while hypoxia (3% PO2) alone had no effect. HVCDFA was consistently observed in both endothelium-intact and -denuded vessels with partial pretone by phenylephrine (PhE) or by other conditions (e.g., K+channel blocker). Patch-clamp study showed no change in the membrane conductance of DFA myocytes by hypoxia. The RhoA-kinase inhibitor Y27632 attenuated HVCDFA. The nitric oxide synthase inhibitor [nitro-L-arginine methyl ester (L-NAME)] and soluble guanylate cyclase inhibitor [oxadiazole quinoxalin (ODQ)] strongly augmented the PhE-pretone, while neither of the agents had effect without pretone. NADPH oxidase type 4 (NOX4) inhibitors (diphenylene iodonium and plumbagin) also potentiated PhE-pretone, which was reversed by NO donor. No additive HVCDFA was observed under the pretreatment with L-NAME, ODQ, or plumbagin. Western blot and immunohistochemistry analysis showed that both NOX4 and endothelial nitric oxide synthase (eNOS) are expressed in smooth muscle layer of DFA. Various mitochondria inhibitors (rotenone, myxothiazol, and cyanide) prevented HVCDFA. From the pharmacological data, as a mechanism for HVCDFA, we suggest hypoxic inhibition of eNOS in myocytes. The putative role of NOX4 and mitochondria requires further investigation. The HVCDFA may prevent imbalance between cardiac output and skeletal blood flow under emergent hypoxia combined with increased sympathetic tone.

AB - In contrast to the conventional belief that systemic arteries dilate under hypoxia, we found that α-adrenergic contraction of rat deep femoral artery (DFA) is largely augmented by hypoxia (HVCDFA) while hypoxia (3% PO2) alone had no effect. HVCDFA was consistently observed in both endothelium-intact and -denuded vessels with partial pretone by phenylephrine (PhE) or by other conditions (e.g., K+channel blocker). Patch-clamp study showed no change in the membrane conductance of DFA myocytes by hypoxia. The RhoA-kinase inhibitor Y27632 attenuated HVCDFA. The nitric oxide synthase inhibitor [nitro-L-arginine methyl ester (L-NAME)] and soluble guanylate cyclase inhibitor [oxadiazole quinoxalin (ODQ)] strongly augmented the PhE-pretone, while neither of the agents had effect without pretone. NADPH oxidase type 4 (NOX4) inhibitors (diphenylene iodonium and plumbagin) also potentiated PhE-pretone, which was reversed by NO donor. No additive HVCDFA was observed under the pretreatment with L-NAME, ODQ, or plumbagin. Western blot and immunohistochemistry analysis showed that both NOX4 and endothelial nitric oxide synthase (eNOS) are expressed in smooth muscle layer of DFA. Various mitochondria inhibitors (rotenone, myxothiazol, and cyanide) prevented HVCDFA. From the pharmacological data, as a mechanism for HVCDFA, we suggest hypoxic inhibition of eNOS in myocytes. The putative role of NOX4 and mitochondria requires further investigation. The HVCDFA may prevent imbalance between cardiac output and skeletal blood flow under emergent hypoxia combined with increased sympathetic tone.

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