Abstract P192: Both Mineralocorticoid Receptor and Angiotensin II type 1 Receptors in the Subfornical Organ Mediate Angiotensin II Induced Reactive Oxygen Species (ROS) in Brain Angiotensinergic Pathways
Activation of angiotensinergic pathways and central aldosterone (aldo)-MR-ENaC-endogenous ouabain (EO)-AT1R pathway play a critical role in Ang II associated hypertension. The SFO contains both MR and AT1R and can relay the signals of circulating Ang II to downstream nuclei such as the PVN, SON and RVLM. We evaluated the effect of knockdown of MR and AT1R specific in the SFO on reactive oxygen species (ROS) production in downstream nuclei. Wistar rats were intra SFO infused with AAV-MR- or AT1aR-siRNA and after 7 days received a sc infusion of Ang II at 500 ng/min/kg for 2 weeks. MR and AT1R expression were measured by real-time qPCR and western blotting. ROS was assessed by DHE staining.
Ang II increased AT1R mRNA expression in the SFO. Both MR- and AT1R-siRNA in the SFO prevented this increase. Ang II decreased MR mRNA but increased protein expression in the SFO. Both MR- and AT1R-siRNA further decreased MR mRNA expression. Ang II significantly increased ROS in the SFO, magno- and parvocellular parts of the PVN, SON and RVLM. Both MR- and AT1R-siRNA in the SFO prevented ROS increases in the PVN and RVLM. In contrast, MR- but not AT1R-siRNA in the SFO prevented the Ang II-induced ROS in the SON. Both MR- and AT1R-siRNA in the SFO prevented most of the Ang II-induced hypertension. These results suggest that aldo-MR signaling in the SFO is needed for the activation of Ang II-AT1R signaling from the SFO to the PVN and RVLM. Considering that only MR-siRNA in the SFO prevents circulating Ang II induced ROS in the SON, activation of aldo-MR signaling from the SFO to the SON may via EO enhance AT1R dependent activation of pre-sympathetic neurons in the PVN, and thereby to Ang II-hypertension.
Author Disclosures: H. Wang: None. R. White: None. B.S. Huang: None. A. Chen: None. M. Ahmad: None. F.H. Leenen: None.
- © 2015 by American Heart Association, Inc.