Cerebral vasoconstriction produced by vasopressin in conscious goats: role of vasopressin V 1 and V 2 receptors and nitric oxide

To examine the role of vasopressin V 1 and V 2 receptors, nitric oxide and prostanoids in the cerebrovascular effects of arginine vasopressin, cerebral blood flow was electromagnetically measured in awake goats. In 16 animals, vasopressin (0.03 – 1 μg), injected into the cerebral circulation, caused increments of resting cerebrovascular resistance which ranged from 18% (0.03 μg, P <0.01) to 79% (1 μg, P <0.01). Desmopressin (0.03 – 1 μg, four goats) did not affect significantly cerebrovascular resistance. The cerebrovascular resistance increases by vasopressin were reduced significantly by the antagonist for vasopressin V 1 receptors d(CH 2 ) 5 Tyr(Me)‐AVP in a rate depending way (five (six goats) and 15 (four goats) μg min −1 ), and by the mixed antagonist for vasopressin V 1 and V 2 receptors desGly‐d(CH 2 ) 5 ‐ D ‐Tyr(Et)Val‐AVP (5 μg min −1 , four goats), and they were not significantly affected by the antagonist for vasopressin V 2 receptors d(CH 2 ) 5 , D‐Ile 2 , Ile 4 ‐AVP (5 μg min −1 , four goats). The inhibitor of nitric oxide synthesis N w ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME, 47 mg kg −1 i.v., five goats) augmented cerebrovascular resistance by 130% ( P <0.01), and for 24 h after this treatment the cerebrovascular effects of vasopressin were potentiated. The inhibitor of cyclo‐oxygenase meclofenamate (6 mg kg −1 i.v., five goats) did not modify significantly resting haemodynamic variables measured or the cerebrovascular effects of vasopressin. Therefore, the vasopressin‐induced cerebral vasoconstriction may be mediated by vasopressin V 1 receptors, without involvement of vasopressin V 2 receptors, and may be modulated by nitric oxide but not by prostanoids.British Journal of Pharmacology (2001) 132 , 1837–1844; doi: 10.1038/sj.bjp.0704034