Nitric oxide (NO) is produced and released in the hypothalamus-neurohypophysial system (HNS) and modulates a wide variety of physiological functions. Angiotensin-II (ANG-II) acts in the HNS to control vasopressin (AVP), oxytocin (OT) release and mean arterial pressure (MAP). We evaluated the central effects of the nitrergic system on the hormonal release and MAP induced by central ANG-II stimulation. Male Wistar rats (±280g) anaesthetized with 2.5% tribromoethanol (1ml/100g body weight, i.p.) had a stainless guide cannula placed into the right lateral ventricle. Six days after surgery, they received an intracerebroventricular (icv) injection of Nw-Nitro-L-arginine methyl ester (L-NAME, 40µg), an inhibitor of NO synthase, L-arginine (20µg), a precursor of NO, or vehicle (0.15M NaCl) and 10 min later they received an icv injection of ANG-II (26ng) or vehicle. Blood samples were collected 5 min after injection of ANG-II for determination of plasma neurohypophysial hormones. MAP was determined during 30 min after ANG-II in another set of rats. The results are reported as means ± SEM. The data were analysed by two way ANOVA followed by Newman-Keuls post hoc test. Differences were considered significant at P<0.05. Rats treated with L-NAME followed by vehicle (n=6) and vehicle followed by ANG-II (n=7) showed, respectively, an increase of plasma AVP (3.1±0.2pg P<0.01 and 4.6±0.4pg P<0.001), OT (12.3±1.5pg P<0.05 and 31.5±5.8pg P<0.001) levels and MAP (14.2±0.7mmHg P<0.001 and 14.6±0.8mmHg P<0.001), compared to the control group (vehicle followed by vehicle n=9, AVP: 1.9±0.2pg, OT: 4.6±0.6pg and MAP: 5.9±0.4mmHg). L-arginine followed by vehicle (n=7) did not modify the hormonal concentrations and MAP. Pre-treatment with L-NAME enhanced the AVP (5.7±0.4pg P<0.01), OT (43.4±5.7pg P<0.05) release and MAP (18.2±0.8mmHg P<0.001) induced by ANG-II (n=6). On the other hand, L-arginine reduced the increase of AVP (3.1±0.3pg P<0.001), OT (17.5±5.2pg P<0.05) secretion and MAP (5.9±0.6mmHg P<0.001) induced by ANG-II (n=7). In conclusion, the present data demonstrate that the inhibition of central nitrergic system facilitates AVP and OT release and the increase of MAP in response to ANG-II, suggesting an inhibitory modulation of NO in the control of neurohypophysial hormone secretion and blood pressure regulation.