INHIBITORY EFFECT OF DUP-753 ON THE DRINKING RESPONSES OF RATS TO CENTRAL ADMINISTRATION OF NORADRENALINE AND ANGIOTENSIN-II AND TO DEHYDRATION

We investigated the effect of losartan (DUP-753) on the dipsogenic res ponses produced by intracerebroventricular (icv) injection of noradren aline (40 nmol/mu l) and angiotensin II (ANG II) (2 ng/mu l) in male H oltzman rats weighing 250-300 g. The effect of DUP-753 was also studie d in animals submitted to water deprivation for 30 h. After control in jections of isotonic saline (0.15 M NaCl, 1 mu l) into the lateral ven tricle (LV) the water intake was 0.2 +/- 0.01 ml/h. DUP-753 (50 nmol/m u l) when injected alone into the LV of satiated animals had no signif icant effect on drinking (0.4 +/- 0.02 ml/h) (N = 8). DUP-753 (50 nmol /mu l) injected into the LV prior to noradrenaline reduced the water i ntake from 2.4 +/- 0.8 to 0.8 +/- 0.2 ml/h (N = 8). The water intake i nduced by injection of ANG II and water deprivation was also reduced f rom 9.2 +/- 1.4 and 12.7 +/- 1.4 ml/h to 0.8 +/- 0.2 and 1.7 +/- 0.3 m l/h (N = 6 and N = 8), respectively. These data indicate a correlation between noradrenergic pathways and angiotensinergic receptors and lea d us to conclude that noradrenaline-induced water intake may be due to the release of ANG II by the brain. The finding that water intake was reduced by DUP-753 in water-deprived animals suggests that dehydratio n releases ANG II, and that AT(1) receptors of the brain play an impor tant role in the regulation of water intake induced by deprivation.