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

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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

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

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    Han, J. A., Seo, E. Y., Kim, H. J., Park, S. J., Yoo, H. Y., Kim, J. Y., Shin, D. M., Kim, J. K., Zhang, Y. H., & Kim, S. J. (2013). Hypoxia-augmented constriction of deep femoral artery mediated by inhibition of eNOS in smooth muscle. American Journal of Physiology - Cell Physiology, 304(1), C78-C88. https://doi.org/10.1152/ajpcell.00176.2012