Vasopressin V-1A receptor antagonism does not reverse adrenocorticotrophin-induced hypertension in the rat

1. The role of arginine vasopressin (AVP) was examined in adrenocorticotrop hin (ACTH)-induced hypertension in Sprague-Dawley rats using the non-peptid e AVP V-1a receptor antagonist OPC 21268. 2. In an acute study, six rats were pretreated with ACTH for 11 days and di rect arterial blood pressure (4 h), plasma osmolality and electrolyte conce ntrations were measured after OPC 21268 gavage. In a chronic study, 40 rats were randomly divided into four groups: (i) sham injection + sham gavage; (ii) ACTH + sham gavage; (iii) sham injection + OPC 21268; or (iv) ACTH + O PC-21268 for 16 days. Systolic blood pressure (SBP), water intake, urine vo lume (UV), urine osmolality and electrolytes, food intake, bodyweight and p lasma osmolality and electrolyte concentrations were measured. 3. In the acute study, direct mean arterial blood pressure did not change w ith OPC 21268 (122 +/- 2 and 120 +/- 3 mmHg at 0 and 240 min, respectively) . 4. In the chronic study, OPC 21268 did not affect ACTH-induced rises in blo od pressure (from 125 +/- 2 (control) to 145 +/- 5 mmHg (group 4) compared with 122 +/- 3 (control) to 149 +/- 5 mmHg (group2)). Water intake and UV i ncreased (from 29 +/- 2 to 83 +/- 6 mL/day; and from 5 +/- 1 to 36 +/- 5 mL /day, respectively) and the change in bodyweight decreased from 0 +/- 2 to -107 +/- 7 g. 5. These results suggest that AVP (at the V-1a receptor) does not play a si gnificant role in the maintenance of ACTH-induced hypertension.