The effects of 6-hydroxydopamine on the disposition of norepinephrine in the rabbit aorta.

Pretreatment of rabbits with 6-hydroxydopamine (6-OHDA; 25 mg/kg i.v. on day 0 plus 50 mg/kg i.v. on day 1, sacrifice on day 4) depleted 95% of the endogenous catecholamines from the rabbit thoracic aorta and heart. A partial recovery of endogenous catecholamines occurred over the next 2 weeks. 6-OHDA pretreatment decreased the cocaine-sensitive accumulation and the binding of l-[3H]norepinephrine (l-[3H]NE) by 85% in the rabbit thoracic aorta. Thus, this pretreatment with 6-OHDA produced an adequate chemical sympathectomy of the rabbit thoracic aorta. The effects of 6-OHDA pretreatment on the accumulation ane metabolism of l-[3H]NE were examined in the isolated adventitia and isolated media of the rabbit aorta to determine the origin of the O-methylated metabolites formed by the isolated adventitia. In the isolated adventitia, 6-OHDA pretreatment decreased the accumulation of l-[3H]NE and the formation of deaminated metabolites by 80%, but the formation of [3H]normetanephrine was increased more than 2-fold. 6-OHDA produced only a slight decrease in the formation of one of the deaminated metabolites of l-[3H]NE by the isolated media. These results are interpreted to mean that in the isolated adventitia most of the accumulation and deamination of l-[3H]NE occurs in the adrenergic nerve terminals whereas most of the O-methylation occurs in the extraneuronal elements of the isolated adventitia.