title: Effects of hypoxia on contractile responses of rabbit aortic strips to transmural electrical stimulation.
abstract: To clarify the effects of hypoxia on adrenergic transmission, we examined the contractile responses of isolated rabbit aortic strips to electrical stimulation, the concentration-response relationships for noradrenaline and KCl, and the electrical stimulation-evoked overflows of total [3H] and [3H]noradrenaline from strips preloaded with [3H]noradrenaline in media equilibrated with gas mixtures containing various concentrations of O2. Contractile responses to electrical stimulation were completely inhibited by tetrodotoxin and alpha-adrenoceptor antagonists such as phentolamine and phenoxybenzamine, but were not affected by indomethacin. When the concentration of O2 in the gas mixture was decreased from 95% to 20%, the contractile responses to electrical stimulation remained unchanged, but as the concentration of O2 was further decreased, the responses were inhibited concentration-dependently. At 0% O2, the response was inhibited by about 80% when compared with control values obtained at 95% O2, and the electrical stimulation-evoked overflows of total [3H] and [3H]noradrenaline into the superfusates were decreased by about 55%. At 0% O2, the concentration-response curve for exogenous noradrenaline was shifted to the right about 50-fold and the maximum response was decreased by 25%. The maximum contractile responses of aortic strips from animals pretreated with reserpine or 6-hydroxydopamine to high KCl were decreased slightly (about 15%). These results suggest that inhibition of adrenergic transmission under hypoxic conditions is mainly the result of a decrease in the stimulus-evoked release of noradrenaline and of a decrease in the affinity of alpha-adrenoceptor for noradrenaline and/or inhibition of signal transduction mechanisms, although hypoxia also causes a slight decrease in the contractility of vascular smooth muscle.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Miwa
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Koshimura
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Orii
authors.forename: M
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D004558:Electric Stimulation; D000860:Hypoxia / Q000503:physiopathology*; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D013779:Tetrodotoxin; D011189:Potassium Chloride; D009638:Norepinephrine