title: Stimulation of angiotensin type 1A receptors on catecholaminergic cells contributes to angiotensin-dependent hypertension.
abstract: Hypertension contributes to multiple forms of cardiovascular disease and thus morbidity and mortality. The mechanisms inducing hypertension remain unclear although the involvement of homeostatic systems, such as the renin-angiotensin and sympathetic nervous systems, is established. A pivotal role of the angiotensin type 1 receptor in the proximal tubule of the kidney for the development of experimental hypertension is established. Yet, other systems are involved. This study tests whether the expression of angiotensin type 1A receptors in catecholaminergic cells contributes to hypertension development. Using a Cre-lox approach, we deleted the angiotensin type 1A receptor from all catecholaminergic cells. This deletion did not alter basal metabolism or blood pressure but delayed the onset of angiotensin-dependent hypertension and reduced the maximal response. Cardiac hypertrophy was also reduced. The knockout mice showed attenuated activation of the sympathetic nervous system during angiotensin II infusion as measured by spectral analysis of the blood pressure. Increased reactive oxygen species production was observed in forebrain regions, including the subfornical organ, of the knockout mouse but was markedly reduced in the rostral ventrolateral medulla. These studies demonstrate that stimulation of the angiotensin type 1A receptor on catecholaminergic cells is required for the full development of angiotensin-dependent hypertension and support an important role for the sympathetic nervous system in this model.
authors.affiliation: Department of Physiology, University of Melbourne, Victoria 3010, Australia. a.allen@unimelb.edu.au.
authors.forename: Nikola
authors.initials: N
authors.lastname: Jancovski
authors.forename: Jaspreet K
authors.initials: JK
authors.lastname: Bassi
authors.forename: David A
authors.initials: DA
authors.lastname: Carter
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Choong
authors.forename: Angela
authors.initials: A
authors.lastname: Connelly
authors.forename: Thu-Phuc
authors.initials: TP
authors.lastname: Nguyen
authors.forename: Daian
authors.initials: D
authors.lastname: Chen
authors.forename: Elena V
authors.initials: EV
authors.lastname: Lukoshkova
authors.forename: Clement
authors.initials: C
authors.lastname: Menuet
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Head
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Allen
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002395:Catecholamines / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D013356:Subfornical Organ / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
chemical_list: D002395:Catecholamines; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II
keywords: blood pressure; brain; receptor, angiotensin, type 1; tyrosine 3-monooxygenase