We examined the role of the sympathetic nervous system in the antihypertensive effect of long-term (4-week) administration of cicletanine (50 mg/100 g in diet) in young (6 week-old) spontaneously hypertensive rats (SHR) fed an 8.0% salt-containing diet. Salt loading accelerated the development of hypertension in young SHR (mean blood pressure [BP]: 158 +/- 3 v 196 +/- 5 mm Hg, P < .01). Although cicletanine did not affect mean BP in non-salt-loaded SHR, it reversed salt-induced hypertension (155 +/- 3 mm Hg, P < .01). Salt loading elevated plasma norepinephrine (NE) (246 +/- 16 v 451 +/- 87 pg/mL, P < .05) but simultaneous administration of cicletanine inhibited the increase in plasma NE with salt loading (234 +/- 12 pg/mL, P < .01). Hexamethonium, a ganglionic blocking agent, produced a greater hypotensive effect in salt-loaded than in non-salt-loaded SHR (-40 +/- 4 v -78 +/- 4 mm Hg, P < .01). In salt-loaded SHR with cicletanine, however, the hypotensive effect of hexamethonium was suppressed compared with salt-loaded SHR without cicletanine (-52 +/- 4 mm Hg, P < .01). Both plasma NE (r = 0.608, P < .01) and decrease in mean BP with hexamethonium (r = -0.798, P < .01) correlated with baseline mean BP. Thus, cicletanine inhibited the salt-induced rise in mean BP of young SHR, possibly through the suppression of enhanced sympathetic nerve activity.