Effects of hypoxia on norepinephrine release and metabolism in dog pulmonary artery.

The effect of low O2 tensions on the release and metabolism of norepinephrine during resting conditions and in response to electrical stimulation was studied in isolated superfused segments of dog pulmonary artery. Liquid chromatography with electrochemical detection was used to measure the release and overflow of endogenous norepinephrine and the content of norepinephrine remaining in the tissue after stimulation. In other preparations, norepinephrine stores were labeled with [3H]norepinephrine, and measurements were made of [3H]norepinephrine and its metabolites (separated by column chromatography) in superfusates. Radiolabeled metabolites of norepinephrine produced intraneuronally (3,4-dihydroxyphenylglycol) and extraneuronally (O-methylated) were quantitated by liquid scintillation spectrometry and the relative importance of neuronal uptake, extraneuronal uptake and of norepinephrine overflow in the disposition of norepinephrine calculated. Hypoxia increased the release and overflow of endogenous norepinephrine. In hypoxic conditions 41% of released norepinephrine was disposed of by overflow from the cleft compared with 27% during normoxia. Neuronal uptake of released norepinephrine was reduced during hypoxia and the intraneuronal metabolism of norepinephrine by monoamine oxidase was almost eliminated.