Effects of hypoxia on contractile responses of rabbit aortic strips to transmural electrical stimulation

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.