Chronic Vasopressin Antagonism in Two-Kidney, One-Clip Renovascular Hypertension

The role of vasopressin (AVP) in the maintenance of hypertension in the rat model of two-kidney, one-clip (2K1C) Goldblatt hypertension was assessed using the nonpeptide orally effective V1a receptor antagonist, OPC-21268. Rats were studied eight weeks after surgery when mean arterial pressure (MAP) was significantly increased in 2K1C rats compared to SHAM operated controls (2K1C 139 ±6, SHAM 106±3, P<0.01). Neither acute (OPC-21268, 30mg/kg) nor chronic (OPC-21268, 30mg/kg twice daily) V1a receptor blockade reduced blood pressure in either 2K1C or SHAM rats. The results of binding kinetic studies confirmed that OPC-21268 was effective at its putative site of action, the V1a receptor in both 2K1C and SHAM rats. These results indicate AVP is not involved in the maintenance of blood pressure in the 2K1C model of renovascular hypertension.