Angiotensin II induces vascular dysfunction without exacerbating blood pressure elevation in a mouse model of menopause-associated hypertension

Javeshghani, D., Sairam, M.R., Neves, M.F., Schiffrin, E.L. and Touyz, R.M. (2006) Angiotensin II induces vascular dysfunction without exacerbating blood pressure elevation in a mouse model of menopause-associated hypertension. Journal of Hypertension, 24(7), pp. 1365-1373. (doi: 10.1097/01.hjh.0000234117.25401.f8)

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.<p></p> 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] (ER[alpha]). Vascular structure (media/lumen ratio) was similar in both groups. Abundance of gp91phox, 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).<p></p> 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 ER[alpha] signaling, than in arterial remodeling and BP elevation.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Touyz, Professor Rhian
• Authors: Javeshghani, D., Sairam, M.R., Neves, M.F., Schiffrin, E.L., and Touyz, R.M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of Hypertension
• ISSN: 0263-6352
• ISSN (Online): 1473-5598