| 20089711 |
Zoer B, Cogolludo AL, Perez-Vizcaino F, De Mey JG, Blanco CE, Villamor E: Hypoxia sensing in the fetal chicken femoral artery is mediated by the mitochondrial electron transport chain. Am J Physiol Regul Integr Comp Physiol. 2010 Apr;298(4):R1026-34. Epub 2010 Jan 20.
Vascular hypoxia sensing is transduced into vasoconstriction in the pulmonary circulation, whereas systemic arteries dilate. Mitochondrial electron transport chain (mETC), reactive O (2) species (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 (Po (2) approximately 2.5 kPa) relaxed the contraction induced by norepinephrine (1 microM). Hypoxia-induced relaxation was abolished or significantly reduced by the mETC inhibitors rotenone (complex I), myxothiazol and antimycin A (complex III), and NaN (3) (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 H (2) O (2) (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 Ca (2+)-activated K (+) channel), and BaCl (2) (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 O (2) sensing in fetal chicken femoral arteries. In contrast, hypoxia-induced relaxation appears not to be mediated by ROS or K (+) channels. |
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