It has been shown that vasopressin receptors are upregulated in the brain and that the central vasopressin pathway is involved in the development of deoxycorticosterone acetate (DOCA)-salt hypertension. However, it is unclear whether central vasopressin, in itself, is essential for this type of hypertension. To clarify this issue, the effect of centrally administered vasopressin on the development of DOCA-salt hypertension was studied in homozygous Brattleboro rats which genetically lack vasopressin. In homozygous Brattleboro rats, treatment with intracerebroventricular infusion of vasopressin (1 ng/h) alone or DOCA-salt (weekly subcutaneous injection of 30 mg/kg deoxycorticosterone acetate and 0.3% NaCl to drink) alone had no effect on systolic blood pressure (SBP). On the other hand, hypertension was partially restored in homozygous Brattleboro rats treated with intracerebroventricular infusion of vasopressin and DOCA-salt (SBP: 175 +/- 4 mmHg), although the magnitude of elevation of SBP was one-third of that in Long Evans rats treated with DOCA-salt (278 +/- 15 mmHg). These hypertensive homozygous Brattleboro rats showed an increase in fluid intake and urinary sodium excretion, as observed in DOCA-salt hypertensive Long Evans rats. These results suggest that central vasopressin is required for the complete development of DOCA-salt hypertension and the mechanism is, in part, due to enhanced sodium intake through the additive effect of central vasopressin and DOCA-salt.