ANGIOTENSIN AT(1) RECEPTOR-MEDIATED VASOPRESSIN RELEASE AND DRINKING ARE POTENTIATED BY AN AT(2) RECEPTOR ANTAGONIST

Stimulation of angiotensin II AT(2) receptors has been shown to inhibit AT(1) receptor-mediated actions in peripheral tissues. The role of AT(2) receptors in the central actions of angiotensin is not well understood. In the present study, plasma vasopressin levels and water intake in response to intracerebroventricular angiotensin II(10 pmol) were determined after intracerebroventricular pretreatment with PD 123177 (1-(4-amino-3-methylphenyl)methyl-5-diphenylacetyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid-2HCl), a selective AT(2) receptor antagonist (10, 100 and 1000 pmol), or with losartan (2-n-butyl-4-chloro-5-hydroxy-methyl-1-2'-(1H-tetrazole-5-yl)biphenyl-4-yl)methylimidazole, potassium salt), a specific AT(1) receptor antagonist (0.2, 2 and 10 nmol). Blood samples for vasopressin determination were drawn 90 s after angiotensin II injection and the drinking response was determined in a time interval of 10 min after intracerebroventricular angiotensin II. Losartan at a dose of 2 nmol or higher completely prevented vasopressin release and drinking response to angiotensin II. The drinking response was already attenuated after pretreatment with the lowest dose of losartan. In contrast, PD 123177 potentiated the angiotensin II-induced vasopressin release (39.7 +/- 2.7 pg/ml after 1000 pmol PD 123177 vs. 21.3 +/- 2.9 pg/ml in vehicle-pretreated controls, P < 0.05). The dipsogenic response to angiotensin II was also potentiated by PD 123177 (9.5 +/- 0.7 ml after 1000 pmol PD 123177 vs. 5.1 +/- 1.3 ml in vehicle-pretreated controls, P < 0.05). Our results suggest that the angiotensin II-induced vasopressin release and drinking, mediated by central AT(1) receptors, are under inhibitory control by central AT(2) receptors.