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

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 (HVC(DFA)) while hypoxia (3% Po(2)) alone had no effect. HVC(DFA) 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 HVC(DFA). 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 HVC(DFA) 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 HVC(DFA). From the pharmacological data, as a mechanism for HVC(DFA), we suggest hypoxic inhibition of eNOS in myocytes. The putative role of NOX4 and mitochondria requires further investigation. The HVC(DFA) may prevent imbalance between cardiac output and skeletal blood flow under emergent hypoxia combined with increased sympathetic tone.

Citation

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. Hypoxia-augmented constriction of deep femoral artery mediated by inhibition of eNOS in smooth muscle. American journal of physiology. Cell physiology. 2013 Jan 1;304(1):C78-88

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PMID: 23099643

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