To determine whether paraventricular nucleus (PVN) can play a role in the hypertension in DOCA/salt-treated rats, DOCA/salt hypertension was produced in PVN lesions and sham-operated rats. In lesioned rats, the development of hypertension was significantly attenuated (day 7: 132 +/- 3 v 157 +/- 5 mm Hg, P less than 0.01; day 14: 132 +/- 3 v 157 +/- 5 mm Hg, P less than 0.01; day 21: 189 +/- 2 v 224 +2- 6 mm Hg, P less than 0.01). Lesions lowered systolic blood pressure in even control rats. Mean blood pressure (mBP) from awake free moving rats was also significantly lower in lesioned DOCA/salt-treated rats than those of sham-operated DOCA/salt-treated rats (155 +/- 14 mm Hg v 193 +/- 13, P less than 0.01), while mBP was not different between lesioned and sham-operated control rats. The reduction of mBP by hexamethonium injections was significantly larger in sham-operated DOCA/salt-treated rats than those of lesioned DOCA/salt rats. (-53 +/- 3% v -45 +/- 2, P less than 0.05). Plasma norepinephrine and epinephrine were significantly elevated in DOCA/salt-treated rats, however, PVN lesions inhibited significantly those elevations. 1-Deaminopenicillamine, 4-valine, 8-D-arginine Vasopressin (dPVDAVP) injections did not affect BP and heart rate in all rats. Body weight, water intake, urine volume, urine Na, K, and vasopressin excretion, and urine osmorality were not altered by lesions. These findings suggest that PVN contributes to development of hypertension in DOCA/salt-treated rats with sympathetic nervous activations.