title: Role of angiotensin-converting enzyme 1 within the median preoptic nucleus following chronic intermittent hypoxia.
abstract: Sustained hypertension is an important consequence of obstructive sleep apnea. An animal model of the hypoxemia associated with sleep apnea, chronic intermittent hypoxia (CIH), produces increased sympathetic nerve activity (SNA) and sustained increases in blood pressure. Many mechanisms have been implicated in the hypertension associated with CIH, including the role of ΔFosB within the median preoptic nucleus (MnPO). Also, the renin-angiotensin system (RAS) has been associated with CIH hypertension. We conducted experiments to determine the possible association of FosB/ΔFosB with a RAS component, angiotensin-converting enzyme 1 (ACE1), within the MnPO following 7 days of CIH. Retrograde tract tracing from the paraventricular nucleus (PVN), a downstream region of the MnPO, was used to establish a potential pathway for FosB/ΔFosB activation of MnPO ACE1 neurons. After CIH, ACE1 cells with FosB/ΔFosB expression increased colocalization with a retrograde tracer that was injected unilaterally within the PVN. Also, Western blot examination showed ACE1 protein expression increasing within the MnPO following CIH. Chromatin immunoprecipitation (ChIP) assays demonstrated an increase in FosB/ΔFosB association with the ACE1 gene within the MnPO following CIH. FosB/ΔFosB may transcriptionally target ACE1 within the MnPO following CIH to affect the downstream PVN region, which may influence SNA and blood pressure.
authors.affiliation: Institute for Cardiovascular and Metabolic Diseases, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas; and.
authors.forename: Katelynn
authors.initials: K
authors.lastname: Faulk
authors.affiliation: Institute for Cardiovascular and Metabolic Diseases, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas; and.
authors.forename: Brent
authors.initials: B
authors.lastname: Shell
authors.affiliation: Institute for Cardiovascular and Metabolic Diseases, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas; and.|American Heart Association, Dallas, Texas.
authors.forename: T Prashant
authors.initials: TP
authors.lastname: Nedungadi
authors.affiliation: Institute for Cardiovascular and Metabolic Diseases, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas; and Tom.Cunningham@unthsc.edu.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011301:Preoptic Area / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D007703:Peptidyl-Dipeptidase A
keywords: angiotensin; hypertension; median preoptic nucleus; sleep apnea