Hypoxia sensing in the fetal chicken femoral artery is mediated by the mitochondrial electron transport chain

Abstract

Vascular hypoxia sensing is transduced into vasoconstriction in the pulmonary circulation, whereas systemic arteries dilate. Mitochondrial electron transport chain (mETC), reactive O2species (ROS), and K+channels have been implicated in the sensing/signaling mechanisms of hypoxic relaxation in mammalian systemic arteries. We aimed to investigate their putative roles in hypoxia-induced relaxation in fetal chicken (19 days of incubation) femoral arteries mounted in a wire myograph. Acute hypoxia (Po2∼2.5 kPa) relaxed the contraction induced by norepinephrine (1 μM). Hypoxia-induced relaxation was abolished or significantly reduced by the mETC inhibitors rotenone (complex I), myxothiazol and antimycin A (complex III), and NaN3(complex IV). The complex II inhibitor 3-nitroproprionic acid enhanced the hypoxic relaxation. In contrast, the relaxations mediated by acetylcholine, sodium nitroprusside, or forskolin were not affected by the mETC blockers. Hypoxia induced a slight increase in ROS production (as measured by 2,7-dichlorofluorescein-fluorescence), but hypoxia-induced relaxation was not affected by scavenging of superoxide (polyethylene glycol-superoxide dismutase) or H2O2(polyethylene glycol-catalase) or by NADPH-oxidase inhibition (apocynin). Also, the K+channel inhibitors tetraethylammonium (nonselective), diphenyl phosphine oxide-1 (voltage-gated K+channel 1.5), glibenclamide (ATP-sensitive K+channel), iberiotoxin (large-conductance Ca2+-activated K+channel), and BaCl2(inward-rectifying K+channel), as well as ouabain (Na+-K+-ATPase inhibitor) did not affect hypoxia-induced relaxation. The relaxation was enhanced in the presence of the voltage-gated K+channel blocker 4-aminopyridine. In conclusion, our experiments suggest that the mETC plays a critical role in O2sensing in fetal chicken femoral arteries. In contrast, hypoxia-induced relaxation appears not to be mediated by ROS or K+channels.