Angiotensin II-induced Desensitization: Role of the Anteroventral Third Ventricle Region
Vento, Peter J.
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Angiotensin II (AngII) engages coordinated behavioral and physiological responses to hypovolemia, and intracerebroventricular (icv) injection of AngII causes increases in water and salt intake. A growing body of research, however, suggests that AngII-stimulated water intake is reduced after repeated icv injections of the peptide. This AngII-induced desensitization is specific to the effects of angiotensin and likely reflects an underlying change in AngII-responsiveness at the level of the receptor. Specifically, our lab has shown that this phenomenon is mediated by the angiotensin type-1 (AT 1 ) receptor and is not the result of a broader behavioral deficit. Still, a neuroanatomical locus for the effects of repeated central AngII administration remains unknown. The anteroventral third ventricle (AV3V) region is an important site for the behavioral and physiological actions of icv AngII and, as such, it is likely that this region similarly mediates the desensitization produced by repeated AngII administration. In support of this hypothesis, repeated injections of AngII into the AV3V region reduced water intake stimulated by an AngII challenge injection given into either the AV3V region or given icv. Furthermore, AT 1 receptor activation in the AV3V region is important for AngII-induced desensitization because pretreatment with the AT 1 receptor antagonist, losartan, into the AV3V region blocked the desensitizing effect of repeated icv AngII. These findings provide further support for a role of the AV3V region in mediating the dipsogenic effects of icv AngII and suggest that this region is critically important for the desensitization that occurs after repeated central injections of AngII.