Abstract P250: Central Mechanisms Mediating Angiotensin II-Salt Hypertension in Rats
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 2nd exp, MR blockers (eplerenone, spironolactone), ENaC blocker (benzamil), AT1R 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 AT1R and ENaC γ mRNA expression in the PVN, and increased AT1R 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 AT1R mRNA expression increases in both PVN and RVLM and central MR-ENaC-AT1R blockade prevents the hypertension, these results suggest that activation of Ang II-AT1R signaling and MR-ENaC pathway in the brain contribute to both Ang II and Ang II-salt hypertension.
Author Disclosures: J. Lu: None. H. Wang: None. M. Ahmad: None. F.H. Leenen: None.
- © 2015 by American Heart Association, Inc.