title: Mineralocorticoid and angiotensin II type 1 receptors in the subfornical organ mediate angiotensin II - induced hypothalamic reactive oxygen species and hypertension.
abstract: Activation of angiotensinergic pathways by central aldosterone (Aldo)-mineralocorticoid receptor (MR) pathway plays a critical role in angiotensin II (Ang II)-induced hypertension. The subfornical organ (SFO) contains both MR and angiotensin II type 1 receptors (AT1R) and can relay the signals of circulating Ang II to downstream nuclei such as the paraventricular nucleus (PVN), supraoptic nucleus (SON) and rostral ventrolateral medulla (RVLM). In Wistar rats, subcutaneous (sc) infusion of Ang II at 500ng/min/kg for 1 or 2weeks increased reactive oxygen species (ROS) as measured by dihydroethidium (DHE) staining in a nucleus - specific pattern. Intra-SFO infusion of AAV-MR- or AT1aR-siRNA prevented the Ang II-induced increase in AT1R mRNA expression in the SFO and decreased MR mRNA. Both MR- and AT1aR-siRNA prevented increases in ROS in the PVN and RVLM. MR- but not AT1aR-siRNA in the SFO prevented the Ang II-induced ROS in the SON. Both MR- and AT1aR-siRNA in the SFO prevented most of the Ang II-induced hypertension as assessed by telemetry. These results indicate that Aldo-MR signaling in the SFO is needed for the activation of Ang II-AT1R-ROS signaling from the SFO to the PVN and RVLM. Activation of Aldo-MR signaling from the SFO to the SON may enhance AT1R dependent activation of pre-sympathetic neurons in the PVN.
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Canada.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Canada.
authors.forename: Bing S
authors.initials: BS
authors.lastname: Huang
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Canada.
authors.forename: Roselyn A
authors.initials: RA
authors.lastname: White
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Canada.
authors.forename: Aidong
authors.initials: A
authors.lastname: Chen
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Canada.
authors.forename: Monir
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Canada. Electronic address: fleenen@ottawaheart.ca.
authors.forename: Frans H H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D000229:Dependovirus; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D011897:Random Allocation; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D013356:Subfornical Organ / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D018161:Receptors, Mineralocorticoid; D000804:Angiotensin II; D000450:Aldosterone
keywords: angiotensin II type 1 receptor; angiotensinergic pathways; brain; mineralocorticoid receptors; reactive oxygen species