Ricerc@Sapienza

Stress is a significant risk factor for essential hypertension and an important modulator of the sympathetic nervous system (SNS). Only in the last years of researches in this field, it was demonstrated that a chronic exposure to social stress directly affects the adaptive immunity by enhancing the peripheral SNS. In our preliminary data, we observed that mice lacking angiotensin 1a receptor (AT1aR) in the paraventricular nucleus of hypothalamus (PVN), obtained by crossing Sim1Cre mice with AT1aRflox mice, are protected from blood pressure increase after chronic angiotensin II (AngII) infusion, indicating that this brain region is important in mediating blood pressure responses. Furthermore, we also observed that the activity of the splenic sympathetic nerve (SSNA) in these mice is reduced as compared to wild type mice after chronic exposure to AngII. More interesting, the PVN is a crucial station mediating stress responses through the activation of the hypothalamic-pituitary¿adrenal axis (HPA).
First, to evaluate the efficacy of the gene deletion, we will realize an ex vivo laser microdissection of PVN and genomic PCR of AT1aR in AT1aRflox-Sim1-Cre+ mice and their control AT1aRflox-Sim1-Cre-. Then, we will subject AT1aRflox-Sim1-Cre mice, and AT1aRwt-Sim1-Cre- mice as controls, to a protocol of chronic stress for 3 weeks and we will measure arterial blood pressure by plethysmography, SSNA by microneurography and splenic immunity by immunohistochemistry. The aim of this project is to explore whether AT1aRs in PVN are important to drive sympathetic outflow and to modulate the activation of splenic immunity, allowing to identify a brain center controlling a specific efferent pathway in stress-induced hypertension.