Unsustained dipsogenic response to chronic central infusion of angiotensin-III in spontaneously hypertensive rats

We evaluated the chronic effect of angiotensin-III (AIII) in the promotion of drinking behavior in spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats, using conscious, freely moving, male, adult animals that had been instrumented with an intracerebroventricular (icv) cannula connected to an osmotic minipump for 7-day infusion. Chronic icv infusion of AIII (5 or 10 pmol/ min) elicited robust, dose-dependent, and Ile⁷-AIII (100 pmol/min; as specific antagonist)-reversible dipsogenesis in both SH and WKY rats, with higher water intake in the former strain. However, the drinking response in the SHRs exhibited a sharp drop after 3 days of AIII infusion, during which acute AIII (80 pmol, icv) challenges also failed to induce dipsogenesis. Chronic icv infusion of bestatin (150 pmol/ min), an aminopeptidase-B inhibitor, did not by itself discernibly affect basal drinking. When combined with AIII (5 or 10 pmol/min), however, bestatin, respectively, suppressed and augmented the dipsogenic response of SH and WKY rats to the heptapeptide. These results suggest that chronic administration of AIII did not produce sustained drinking behavior in SHRs, possibly because of the development of early desensitization of the angiotensin receptors.