Uptake and metabolism of norepinephrine by endothelium of dog pulmonary artery.

The contribution of endothelium of dog pulmonary artery to the extraneuronal metabolism of norepinephrine was determined. Pulmonary artery was cut into helical strips; the endothelium was removed from half of the strips by gently stroking them with a wooden applicator stick. All strips were immersed in l-[3H]norepinephrine (2 X 10(-7) M) and mounted for superfusion. Superfusate was collected continuously before, during, and after electrical stimulation (10 V, 2 ms, 2 Hz). Column chromatography was used to separate [3H]norepinephrine and its radiolabeled metabolites in superfusate. Quantitation was by liquid scintillation spectrometry. Previous studies have established that 3,4-dihydroxyphenylglycol is of neuronal origin and that O-methylated metabolites are of extraneuronal origin. Since cocaine prevented neuronal uptake of norepinephrine, the reduction in metabolites of norepinephrine of extraneuronal origin in arteries with endothelium removed represented the contribution of endothelium to extraneuronal metabolism. O-Methylated metabolites were decreased from 3.50 to 2.17 X 10(3) dpm/2 ml of superfusate during basal conditions preceding electrical stimulation and from 11.16 to 6.94 X 10(3) dpm/2 ml of superfusate during electrical stimulation when endothelium had been removed. Decreases in extraneuronal metabolite production continued throughout the basal periods following stimulation. These studies suggest that in small pulmonary artery a substantial amount of the total norepinephrine that is released at the neuroeffector junction may be metabolized following uptake into endothelium.