To determine whether the vasopressor and antidiuretic actions of
arginine vasopressin (AVP) may participate in the development of
salt-induced
hypertension, we examined the long-term effects of AVP V1 and
V2 receptor antagonists on blood pressure (BP) in Dahl-Iwai
salt-sensitive (DS) and
salt-resistant (DR) rats. From age 7 weeks, DS and DR rats were fed a diet containing 8% NaCl, alone (control group); 8% NaCl and 1%
OPC-21268 (V1 antagonist-treated group); or 8% NaCl and 0.05%
OPC-31260 (V2 antagonist-treated group). The pressor response to AVP was significantly inhibited in DS rats treated with
OPC-21268. Urinary volume and water intake were significantly increased by administration of
OPC-31260; this increase was greater in DR rats than in DS rats. Indirect BP measurements obtained using tailcuff plethysmography showed that DS but not DR rats developed
hypertension when fed high-
salt diets. However, chronic treatment with either
OPC-21268 or
OPC-31260 did not alter the course of
hypertension in DS rats, despite the effective blocking actions of these antagonists. This finding also was confirmed by direct BP measurements. Our results indicate that even if AVP plays a role in
salt-induced
hypertension peripheral blockade of either subtype of AVP receptors does not prevent the development of
hypertension in DS rats.