title: Angiotensin II induces vascular dysfunction without exacerbating blood pressure elevation in a mouse model of menopause-associated hypertension.
abstract: BACKGROUND
  Follitropin-receptor knockout (FORKO) mice are estrogen-deficient, hyperandrogenic and exhibit features of menopause and elevated blood pressure (BP). Because the renin-angiotensin system has been implicated in menopause-associated hypertension, we questioned whether angiotensin II (Ang II) challenge would further increase BP in FORKO mice and whether this is associated with cardiovascular remodeling and inflammation.
  
  
  RESULTS
  Ang II (400 ng/kg per min) increased BP, assessed by radiotelemetry, similarly in female FORKO and wild-type (WT) mice. Acetylcholine-induced vasodilation was attenuated and Ang II-induced contraction was enhanced in FORKO mice (P < 0.05). This was associated with increased expression of vascular Ang type 1 receptors (AT1R) and estrogen receptor alpha (ERalpha). Vascular structure (media/lumen ratio) was similar in both groups. Abundance of gp91, nitrotyrosine formation and superoxide production, indices of inflammation and cardiac collagen content were increased in Ang II-treated FORKO compared to Ang II-treated WT mice (P < 0.05).
  
  
  CONCLUSIONS
  Thus, in FORKO mice Ang II exacerbates endothelial dysfunction, augments contractility, increases oxidative stress, and promotes cardiac fibrosis without worsening vascular remodeling or BP elevation compared to Ang II-treated WT controls. Our findings suggest that in FORKO mice Ang II may be more important in influencing vascular tone and endothelial function, possibly through oxidative stress and altered ERalpha signaling, than in arterial remodeling and BP elevation.
authors.affiliation: CIHR Multidisciplinary Research Group on Hypertension, Canada.
authors.forename: Danesh
authors.initials: D
authors.lastname: Javeshghani
authors.forename: M Ram
authors.initials: MR
authors.lastname: Sairam
authors.forename: Mario Fritsch
authors.initials: MF
authors.lastname: Neves
authors.forename: Ernesto L
authors.initials: EL
authors.lastname: Schiffrin
authors.forename: Rhian M
authors.initials: RM
authors.lastname: Touyz
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001795:Blood Pressure Determination / Q000379:methods; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D018384:Oxidative Stress / Q000502:physiology; D017698:Postmenopause / Q000502:physiology; D011945:Receptors, Angiotensin / Q000502:physiology; D011962:Receptors, FSH / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D013686:Telemetry / Q000379:methods
chemical_list: D011945:Receptors, Angiotensin; D011962:Receptors, FSH; D000804:Angiotensin II