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 (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 plumbag...