Effects of angiotensin II and its blockers Sar1-lle8-angiotensin II and DuP 753 on drinking in ducks in relation to properties of subfornical organ neurons

Abstract

Properties of systemically applied angiotensin II in stimulating water intake of normally hydrated ducks were studied and the results compared with properties of angiotensin II-responsive neurons of the subfornical organ which are considered as targets for circulating angiotensin II acting as a dipsogen. Following intravenous infusion of hypertonic saline (2000 mosmol.kg-1 at 0.3 ml.min-1 for 1 h), intravenous infusion of 0.3 ml.min-1 isotonic saline with angiotensin II (200 ng.min-1), starting 1 h later, stimulated drinking in each case at an angiotensin II plasma level of about 1400 pg.ml-1. Without hypertonic priming, the same angiotensin II infusion did not stimulate drinking in each experiment; however, if effective, repeated infusions of ANGII induced stable dipsogenic responses. Angiotensin II infusions did not alter plasma levels of antidiuretic hormone. Sar1-Ile8-angiotensin II, a non-selective angiotensin II antagonist, acted weakly as a partial agonist when infused at a dose 200-fold higher than angiotensin II and effectively blocked the dipsogenic action of angiotensin II; this corresponds to the inhibition of angiotensin II-induced excitation by Sar1-Ile8-angiotensin II observed in duck subfornical organ neurons. DuP 753 (losartan), an angiotensin II antagonist specifically blocking AT1 receptors in mammals, had equivocal effects on angiotensin II-induced drinking in ducks at rates 50- and 200-fold higher than angiotensin II, which corresponds to the weak inhibitory action of this compound on angiotensin II-induced neuronal excitation in the duck SFO. Blood pressure was only marginally elevated by the applied angiotensin II dose and Sar1-Ile8-angiotensin II had no effect.

Angiotensin, Thirst, and Sodium Appetite

“…In ducks, how-hibited drinking, suggesting that [p-NH 2 -Phe 6 ]ANG II-induced drinking is mediated by AT 1 and not AT 2 receptors. ever, the effects of losartan on intravenous ANG II-induced drinking were equivocal when infused intrave-PD-123319 also inhibited drinking, but this was an effect of PD-123319 pretreatment shown in response to all other nously at rates 50 and 200 times higher than ANG II (535).…”

“…(1-100 mg/100 g), whereas fish that live exclusively in drank in response to intravenous ANG II (200 ng/min), but without hypertonic priming, ANG II did not always fresh water or seawater did not respond (311). Among euryhaline fish, the Japanese eel, Anguilla japonica, stimulate drinking (535). The domestic chicken appears to be less sensitive than pigeon to systemic ANG II, but drank in response to injection of ANG II (100 ng-100 mg)…”

“…In the are important for ligand binding and that account for the sensitivity of AT 1 receptors to inactivation by sulfhydryl-duck, however, intravenous infusion of the 8-substituted analog sarile inhibited intravenous ANG II-induced drink-reducing agents such as dithiothreitol. In the rat, the AT 1 receptor has been further subdivided by cloning and se-ing when the dose infused was 200 times higher than that of ANG II (535).…”