PARAVENTRICULAR NUCLEUS ADMINISTRATION OF DUP753 OR PD123319 INHIBITSTHE EFFECTS OF ANGIOTENSIN ON WATER AND SODIUM-INTAKE

We determined the effects of DuP753 and PD123319 (both nonpeptides and selective antagonists of the AT(1) and AT(2) angiotensin receptors, r espectively), and [Sar(1), Ala(8)]ANG II (a non-selective peptide anta gonist of angiotensin receptors) on water and 3%NaCl intake induced by administration of angiotensin II (ANG II) into the paraventricular nu cleus (PVN) of sodium-depleted Holtzman rats weighing 250-300 g. Twent y hours before the experiments, the rats were depleted of sodium using furosemide (10 ng/rat, sc). The volume of drug solution injected was 0.5 mu l over a period of 10-15 sec. Water and sodium intake were meas ured at 0.25, 0.5, 1.0 and 2.0 h. Pre-treatment with DuP753 (14 rats) at a dose of 60 ng completely abolished the water intake induced by in jection of 12 ng of ANG II (15 rats) (6.4 +/- 0.6 vs 1.4 +/- 0.3 ml/2 h), where [Sar(1), Ala(8)]ANG II (12 rats) and PD123319 (10 rats) at t he doses of 60 ng partially blocked water intake (6.4 +/- 0.6 vs 2.9 /- 0.5 and 2.7 +/- 0.2 ml/2 h, respectively). In the same animals, [Sa r(1), Ala(8)]ANG II, DuP753, and PD123319 blocked the sodium intake in duced by ANG II (9.2 +/- 1.6 vs 3.3 +/- 0.6, 1.8 +/- 0.3, and 1.4 +/- 0.2 ml/2 h, respectively). These results indicate that both DuP753 and PD123319, administered into the PVN, blocked the water and sodium int ake induced by administration of ANG II into the same site.