From brain to kidney: Central AT1 receptors and sympathetic nervous system interaction in sodium excretion mechanisms

Abstract

Central angiotensin II through AT1 receptors (AT1-R), closely interact with sympathetic nervous system (SNS) in the maintenance of renal sodium equilibrium under normal and pathological conditions. Our aim was to unmask the brain AT1-R role in the renal sodium excretion mechanisms and the interaction with the SNS. For these purposes, male Wistar rats with renal nervous ablation/sham and implanted with bilateral cannulae in lateral ventricle, received normosodic (0.4 %) or hypersonic (4 %) diet in metabolic cages for 5 days. The surgical procedures were performed under ketamine/xylaxine (75/5 mg/kg i.p.) anesthesia. The urine was daily collected and water intake was register along the experiment. On day 6 the animals received saline/losartan (AT1- R antagonist 4ug/1 μl) intracerebrally and sacrificed 12 hours later. The parameters analyzed were; in urine: volume, sodium, potassium, water, creatinine and osmolarity to evaluate kidney function; at brain: c-Fos expression in paraventricular (PVN), supraoptic (SON) and subfornical (SFO) nucleus and vasopressin by immunohistochemistry. The data were analyzed by factorial ANOVA. The effects of central AT1-R and the interaction with SNS were observed on water intake and sodium and water excretion. Renal sodium excretion and water intake are under central AT1-R activation depending on renal nervous integrity. AT1-R blockade blunted the increased c-Fos expression induced by hypersodic diet in vasopressinergic neurons (PVN and SON). We conclude that SNS regulates the complex interaction between central angiotensin II, through AT1-R, and vasopressinergic neurons at SON and PVN under sodium overload conditions.