Angiotensin II (ANG II) is involved in the renal sodium homeostasis in close relation with sympathetic nervous system (SNS) under normal and pathological conditions. Vasopressin (AVP), a hormone that modulates renal sodium and water reabsorptionis synthetized and released from supraoptic (SON) and paraventricular nucleus (PVN) under ANG II influence. We hypothesized that brain ANG II AT1 receptors (AT1-R) regulate renal sodium and water reabsorption and excretion through SNS. In this study male Wistar rats with renal denervation/sham and fed with hypersodic (4%) or normal (0.4%) diet were evaluated during 5 days in metabolic cages. On day 5 were injected in lateral ventricle with losartan (AT1-R antagonist) and sacrificed 12 hours later. The urine was daily collected, blood samples and brains were obtained for determinations. The parameters analyzed were: a) c-Fos immunoreactivity in SON, PVN, subfornical (SFO) and organum vasculosum of the lamina terminalis nucleus (OVLT), b) c-Fos-AVP immunoreactivity in SON in sham group, c) sodium and water intake, d) water, sodium and creatinine excretion. Results: c-Fos expression in SFO, OVLT and PVN was differentially affected by hypersodic diet or losartan depending on renal nerve integrity. In sham animals losartan prevented the hypersodic diet effects in water intake, c-Fos and AVP positive neurons in SON. Renal denervation modified the effect of hypersodic diet in water intake, urinary volume and creatinine excretion; losartan prevented these alterations. Food intake was similar in all groups. Our results suggest that brain AT1-R regulate renal sodium and water reabsorption through SNS in close interaction with AVP.

Decreased serotonin (5-HT) has long been linked to increased aggressive behavior. Tryptophan hydroxylase (TPH) is an enzyme involved in 5-HT synthesis and para-chlorophenylalanine (pCPA) inhibits its activity. TPH2 mRNA expression presence has been mainly described in the raphe complex rodent’s brain. 5-HT-producing neurons in the raphe project their axons to olfactory bulb, considered to be a relevant structure in rodents for establishing social interactions, including aggressive behavior. However, the relationship between olfactory bulb and aggression in a pCPA 5-HT depletion model has not been studied. Moreover, receptor subunit GABA α1 has been found in the olfactory bulb and 5-HT depletion could affect GABAA receptor expression in different brain areas. Thus, our aim was to evaluate aggressive behavior, serotonergic activity, the TPH2 and GABAA α1 mRNA expression, in the olfactory bulb, after a single pCPA (300mg/kg) or vehicle i.p. administration in male rats. Aggression was tested using a resident intruder test. Sequentially, the olfactory bulb was obtained, and neurochemical and molecular techniques were used to measure 5-HT, 5-HIAA, TPH2, and GABAA α1 mRNA expression respectively. pCPA administration increased aggressive behavior parameters, without affecting locomotion, nonsocial or social interaction. 5-HT levels were decreased after pCPA administration, as well as its turnover rate, although there were no significant changes in 5-HIAA. TPH2 mRNA expression was increased. GABAA α1 mRNA expression was increased in the olfactory bulb. Our results apport evidence to the serotonergic deficiency hypothesis of aggression and highlight olfactory bulb role as an important structure for understanding aggressive behavior neurobiological complexity.