Inhibition of norepinephrine release from vascular adrenergic neurons by oral administration of beta-blocker in DOCA-salt hypertension. The ability of a beta-blocker to inhibit vascular sympathetic nerve activity associated with hypertension was studied in DOCA-salt hypertension in rats. A seven week treatment of DOCA and salt resulted in a significant increase in the systolic blood pressure of the uninephrectomized rats. The administration of propranolol (40 mg/L and 80 mg/L in drinking water) had little effect on the development of hypertension. After a three week administration of propranolol, perfused mesenteric vasculatures were prepared in vitro, and endogenous norepinephrine release as well as vascular responsiveness were examined. Endogenous norepinephrine and pressor responses during periarterial nerve stimulation were greater in the untreated DOCA-salt hypertensive rats than in the normotensive rats. In the DOCA-salt hypertensive rats treated with propranolol, the stimulation-evoked norepinephrine release and pressor responses were significantly attenuated, at both doses, compared with the untreated DOCA-salt hypertensive rats. These results demonstrate that propranolol inhibited the vascular sympathetic nerve activity in DOCA-salt hypertensive rats. This occurrence suggests a possible role of presynaptic beta-adrenoceptors in the regulation of sympathetic tone in DOCA-salt hypertension. 