Abstract P142: Regulation of Brain Derived Neurotrophic Fractor (BDNF) Expression by Angiotensin II in the Adrenals and the Brain
Circulating Ang II activates central angiotensinergic pathways, and an amplifying aldosterone (aldo)-MR-ENaC-AT1R neuromodulatory pathway which are critical for several forms of hypertension. We hypothesized that in addition Ang II increases BDNF expression in both the CNS and adrenal which plays a balancing role against Ang II excitatory actions. In the 1st exp, Wistar rats were sc infused with Ang II at the high dose of 500 ng/kg/min for 7days. In the 2nd exp, rats were treated with regular salt diet (0.4% NaCl), high salt diet (2% NaCl), sc Ang II at the low dose of 150 ng/kg/min, or sc Ang II with high salt diet for 14 days. In the 3rd exp, MR blockers (eplerenone, spironolactone), ENaC blocker (benzamil), AT1R blocker (losartan) or vehicles (Veh) were icv infused combined with Ang II-salt. In the 4th exp, rats were sc infused with aldo (1μg/hr) with saline as drinking fluid. mRNA levels of BDNF were measured by real-time qPCR. In the adrenals, Ang II dose-related increased BDNF mRNA, and Ang II-salt further enhanced BDNF mRNA. High dose Ang II increased BDNF mRNA in the RVLM but not in the PVN. Central blockades markedly decreased Ang II-salt induced BDNF expression in the adrenal cortex. In contrast, saline alone or aldo-saline decreased BDNF mRNA in the adrenal cortex with no effect in the PVN. Central blockades lower Ang II-salt induced BDNF expression in the adrenal, indicating that a central regulatory mechanism plays a role in adrenal BDNF expression. Activation of BDNF by Ang II -modulated by salt-, may provide an important balancing mechanism both centrally and peripherally for Ang II associated hypertension.
Author Disclosures: H. Wang: None. J. Lu: None. M. Ahmad: None. F.H. Leenen: None.
- © 2015 by American Heart Association, Inc.