Repeated administration of angiotensin II reduces its dipsogenic effect without affecting saline intake

Angiotensin II (Ang II) acts at central type 1 (AT(1)) receptors to increase intake of water and saline. In vitro studies demonstrated rapid desensitization of the AT(1) receptor after Ang II exposure, and behavioural studies in rats suggest that exposure to Ang II decreases the dipsogenic potency of subsequent Ang II. Nevertheless, the effect of repeated Ang II injections on saline intake remains untested, and a reliable protocol for examining this purported behavioural desensitization has not emerged from the literature. To address these issues, we established a reliable approach to study Ang II-induced dipsetic desensitization and used this approach to test the requirement of central AT(1) receptors and the specificity of the effect for water intake. Rats given a treatment regimen of three injections of Ang II (300 ng, intracerebroventricular), each separated by 20 min, drank less water than control rats after a subsequent test injection of Ang II. The effect was relatively short lasting, dependent on the dose and timing of Ang II, and was almost completely blocked by the AT(1) receptor antagonist losartan. In further testing, when rats were given access to both water and 1.5% saline, animals that received an Ang II treatment regimen drank less water than control animals, but saline intake was unaffected. These data support previous suggestions that Ang II-induced water and saline intakes are separable. Given the role of G protein uncoupling in desensitization of the AT(1) receptor, these data are consistent with the emerging hypothesis that AT(1) receptor G protein-dependent intracellular signalling pathways are more relevant for water, but not saline, intake.