The effects of idazoxan and other α2‐adrenoceptor antagonists on urine output in the rat

Abstract

In normally‐hydrated Wistar rats the α2‐adrenoceptor antagonist, idazoxan (1, 3, 10 mg kg−1 i.p.), increased urine output during the 6 h following injection. The more selective and specific α2‐adrenoceptor antagonist, RX811059 (0.3, 1, 3 mg kg−1 i.p.), and the peripherally‐acting α2‐adrenoceptor antagonist, L‐659,066 (1, 3, 10 mg kg−1 i.p.), had no effect on urine output in normally‐hydrated animals. In rats given a 25 ml kg−1 water‐load orally, idazoxan (10 mg kg−1, i.p.) produced an initial antidiuretic response which was followed by an increase in urine output which was apparent 4 and 6 h after drug administration. RX811059 (1, 3 mg kg−1 i.p.) and L‐659,066 (3, 10 mg kg−1 i.p.) significantly decreased urine output in water‐loaded rats in the 2 h after injection. The antidiuretic effects of L‐659,066 were attenuated in Brattleboro rats which are deficient in vasopressin; only the highest dose (10 mg kg−1 i.p.) decreased urine output, and this was only a small response in comparison with its virtual abolition of urine output in water‐loaded Wistar rats. The results with the selective α2‐adrenoceptor antagonists in Wistar and Brattleboro rats suggest that α2‐adrenoceptors in the periphery may play a physiological role in the control of water balance through a mechanism which involves vasopressin. The paradoxical diuretic effects of idazoxan contrast with the effects of the other α2‐adrenoceptor antagonists and therefore may be attributed to a property of this compound unrelated to α2‐adrenoceptor blockade. 1992 British Pharmacological Society