title: Angiotensin II type 1a receptors in subfornical organ contribute towards chronic intermittent hypoxia-associated sustained increase in mean arterial pressure.
abstract: Sleep apnea is associated with hypertension. The mechanisms contributing to a sustained increase in mean arterial pressure (MAP) even during normoxic awake-state remain unknown. Rats exposed to chronic intermittent hypoxia for 7 days, a model of the hypoxemia associated with sleep apnea, exhibit sustained increases in MAP even during the normoxic dark phase. Activation of the renin-angiotensin system (RAS) has been implicated in chronic intermittent hypoxia (CIH) hypertension. Since the subfornical organ (SFO) serves as a primary target for the central actions of circulating ANG II, we tested the effects of ANG II type 1a receptor (AT1aR) knockdown in the SFO on the sustained increase in MAP in this CIH model. Adeno-associated virus carrying green fluorescent protein (GFP) and small-hairpin RNA against either AT1aR or a scrambled control sequence (SCM) was stereotaxically injected in the SFO of rats. After recovery, MAP, heart rate, respiratory rate, and activity were continuously recorded using radiotelemetry. In the normoxic groups, the recorded variables did not deviate from the baseline values. Both CIH groups exhibited significant increases in MAP during CIH exposures (P < 0.05). During the normoxic dark phase in the CIH groups, only the SCM-injected group exhibited a sustained increase in MAP (P < 0.05). The AT1aR-CIH group showed significant decreases in FosB/ΔFosB staining in the median preoptic nucleus and the paraventricular nuclei of the hypothalamus compared with the SCM-CIH group. Our data indicate that AT1aRs in the SFO are critical for the sustained elevation in MAP and increased FosB/ΔFosB expression in forebrain autonomic nuclei associated with CIH.
authors.affiliation: Department of Integrative Physiology and Anatomy, and Cardiovascular Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Saxena
authors.affiliation: Department of Integrative Physiology and Anatomy, and Cardiovascular Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Little
authors.affiliation: Department of Integrative Physiology and Anatomy, and Cardiovascular Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas.
authors.forename: T Prashant
authors.initials: TP
authors.lastname: Nedungadi
authors.affiliation: Department of Integrative Physiology and Anatomy, and Cardiovascular Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas Tom.Cunningham@unthsc.edu.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D001794:Blood Pressure; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D012891:Sleep Apnea Syndromes / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D013356:Subfornical Organ / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D044140:Receptor, Angiotensin, Type 1
keywords: AT1aR; angiotensin receptor; chronic intermittent hypoxia; obstructive sleep apnea; subfornical organ