Abstract
We evaluated the dipsogenic effects of angiotensin II (Ang II) in relation to the steady-state level of the endogenous reninangiotensin system (RAS) by measuring water intake in 22 trained dogs during three 20 min intravenous (i.v.) infusions of [Ile5] Ang II (10, 15 and 50ng/kg/min). Measurements obtained in normally hydrated (NHyd) dogs were compared with those obtained in dogs pretreated as follows: 1) 24hr water deprivation (WD); 2) WD combined with chronic blockade of the RAS (300mg/day×3 days of SQ 14225) (WD+SQ); and 3) 48hr after bilateral nephrectomy (BNX). Both WD and WD+SQ were given water before Ang II infusion. Plasma renin activity (PRA) and serum and CSF electrolytes (cisterna magna catheter) were measured. All treatments caused a significant (p<0.05) increase in CSF sodium (Na+) that was not paralleled by hypernatremia in BNX dogs (142±1 vs 144±1mEq/L in NHyd). WD and WD+SQ caused a 2- and 12-fold increase in PRA, respectively; PRA was not detectable in BNX. Suppression of blood Ang II by WD+SQ produced a reduced latency and significant enhancement of the thirst behavior elicited by Ang II at all doses; however, i.v. Ang II did not elicit drinking in the WD state. Furthermore, in BNX, the same phenomenon as in WD+SQ was observed. These data are compatible with the concept that endogenous levels of Ang II play a key role in regulating drinking behavior. However, these findings do not negate the possibility that Ang II acts synergistically with CSF Na+, but not plasma Na+, to modulate drinking behavior.
