Central Mechanisms Mediating Ang II-Salt Hypertension

• Main Author: Lu, Jiao
• Other Authors: Leenen, Frans
• Language: en
• Published: Université d'Ottawa / University of Ottawa 2016
• Subjects: angiotensin II; salt; hypertension; aldosterone; CNS; AT1R; PVN
• Online Access: http://hdl.handle.net/10393/34811; http://dx.doi.org/10.20381/ruor-6062

Abstract Statement of problem Plasma angiotensin II (Ang II) increases blood pressure (BP) through the activation of brain angiotensinergic pathways and the aldosterone-mineralocorticoid receptors (MR)- epithelial Na+ channel (ENaC)-endogenous ouabain (EO) pathway. The response of BP to circulating Ang II is enhanced by high salt intake, but the central mechanisms mediating this elevated response are not known. Methods of investigation Study 1) Male Wistar rats were divided into 4 groups and treated with regular salt diet (0.4% NaCl), high salt diet (2% NaCl), sc Ang II infusion (150 ng/kg/min), or sc Ang II infusion together with 2% salt diet for 14 days; plasma aldosterone and corticosterone levels, CYP11B2 mRNA in adrenal cortex and the mRNA levels of Ang II type 1 receptors (AT1R), CYP11B1 (11-β hydroxylase), CYP11B2 (aldosterone synthase), MR, 11βHSD2, ENaC α, ENaC β and ENaC γ in the subfornical organ (SFO), paraventricular nucleus (PVN), supraoptic nucleus (SON) and rostral ventrolateral medulla (RVLM) were measured. Study 2) MR blockers (eplerenone, spironolactone), ENaC blocker (benzamil), AT1R blocker (losartan) or vehicles were centrally infused in rats treated with Ang II plus high salt, and BP and heart rate (HR) were recorded by telemetry; plasma aldosterone and corticosterone levels and CYP11B2 mRNA expression in adrenal cortex were measured. Major findings Ang II alone caused a small increase in BP. Ang II together with 2% salt diet markedly increased the BP and plasma aldosterone level. Sc Ang II decreased 11βHSD2 and MR mRNA expression in the PVN, increased AT1R and ENaC γ expression in the PVN, and increased AT1R mRNA expression in the RVLM. Other genes tested in the four brain nuclei were not affected by sc Ang II or high salt diet. BP and plasma aldosterone increases in response to Ang II and salt, as well as CYP11B2 mRNA expression in adrenal cortex, were largely prevented by central infusion of eplerenone, spironolactone, benzamil or losartan. Main conclusion BP and plasma aldosterone responses to Ang II-salt are under the control of central mechanisms, and MR-AT1R activation in the brain plays a critical role in Ang II-salt induced hypertension.