title: 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 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.
authors.affiliation: University Hospital Maastricht, P. Debyelaan 25, AZ Maastricht, The Netherlands.
authors.forename: Bea
authors.initials: B
authors.lastname: Zoer
authors.forename: Angel L
authors.initials: AL
authors.lastname: Cogolludo
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Vizcaino
authors.forename: Jo G R
authors.initials: JG
authors.lastname: De Mey
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Blanco
authors.forename: Eduardo
authors.initials: E
authors.lastname: Villamor
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002642:Chick Embryo / Q000098:blood supply / Q000502:physiology*; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology*; D005263:Femoral Artery / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D000860:Hypoxia / Q000139:chemically induced / Q000503:physiopathology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009566:Nitrates / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009566:Nitrates; D017382:Reactive Oxygen Species; D012402:Rotenone; D000968:Antimycin A; D019789:Tetraethylammonium; C031618:sodium nitrate; D009638:Norepinephrine