Abstract P250: Central Mechanisms Mediating Angiotensin II-Salt Hypertension in Rats

Abstract

Circulating Ang II causes persistent activation of brain angiotensinergic pathways through a neuromodulatory aldosterone (aldo)-mineralocorticoid receptors (MR)-epithelial Na + channel (ENaC)-ouabain pathway. The response of BP to circulating Ang II is enhanced by high salt intake. To evaluate the central mechanisms that mediate Ang II-salt induced hypertension, Wistar rats were treated with regular salt diet (0.4% NaCl), high salt diet (2% NaCl), sc Ang II (150 ng/kg / min), or sc Ang II with high salt diet for 14 days. In the 2 nd exp, MR blockers (eplerenone, spironolactone), ENaC blocker (benzamil), AT 1 R blocker (losartan) or vehicles (Veh) were icv infused combined with Ang II-salt. BP was recorded by telemetry. Gene expression was assessed by real-time qPCR. Plasma Ang II and tissue aldosterone were measured by RIA. Ang II alone caused a small increase in MAP (112±1 vs 99±1 mmHg), and BP was markedly increased by Ang II-salt (152±4 mmHg, P<0.05 vs. others). BP increases to Ang II-salt were largely inhibited by central infusion of MR blockers (103±2mmHg), benzamil (100±3mmHg) or losartan (98±4mmHg). Ang II alone or together with salt decreased 11βHSD2 and MR mRNA expression but increased AT 1 R and ENaC γ mRNA expression in the PVN, and increased AT 1 R mRNA level in the RVLM. Sc Ang II or high salt diet had no effect on mRNA levels of CYP11B1, B2, ENaC α or β in the PVN or RVLM. Considering that AT 1 R mRNA expression increases in both PVN and RVLM and central MR-ENaC-AT 1 R blockade prevents the hypertension, these results suggest that activation of Ang II-AT 1 R signaling and MR-ENaC pathway in the brain contribute to both Ang II and Ang II-salt hypertension.