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The effects of idazoxan and other α 2 ‐adrenoceptor antagonists on urine output in the rat
Author(s) -
Jackson Helen C.,
Griffin Ian J.,
Birkett Sonia D.,
Nutt David J.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14353.x
Subject(s) - idazoxan , endocrinology , antagonist , medicine , diuretic , antidiuretic , urine , chemistry , vasopressin , urine osmolality , vasopressin antagonists , prazosin , receptor
1 In normally‐hydrated Wistar rats the α 2 ‐adrenoceptor antagonist, idazoxan (1, 3, 10 mg kg −1 i.p.), increased urine output during the 6 h following injection. 2 The more selective and specific α 2 ‐adrenoceptor antagonist, RX811059 (0.3, 1, 3 mg kg −1 i.p.), and the peripherally‐acting α 2 ‐adrenoceptor antagonist, L‐659,066 (1, 3, 10 mg kg −1 i.p.), had no effect on urine output in normally‐hydrated animals. 3 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. 4 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. 5 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. 6 The results with the selective α 2 ‐adrenoceptor antagonists in Wistar and Brattleboro rats suggest that α 2 ‐adrenoceptors in the periphery may play a physiological role in the control of water balance through a mechanism which involves vasopressin. 7 The paradoxical diuretic effects of idazoxan contrast with the effects of the other α 2 ‐adrenoceptor antagonists and therefore may be attributed to a property of this compound unrelated to α 2 ‐adrenoceptor blockade.