Altered vascular reactivity in mice overexpressing adipocyte mineralocorticoid receptors - role of oxidative stress and Rho kinase

Nguyen Dinh Cat, A., Callera, G. E., Antunes, T. T., Montezano, A. C., He, Y., Jenkins, C., Carter, A., Jaisser, F. and Touyz, R. M. (2013) Altered vascular reactivity in mice overexpressing adipocyte mineralocorticoid receptors - role of oxidative stress and Rho kinase. Hypertension, 62(3 Sup), A66.

Abstract

Aldosterone (aldo) plays a role in obesity and cardiovascular diseases, such as hypertension. We previously demonstrated that adipocyte-derived factors regulate vascular function and vascular smooth muscle cells signaling. Moreover, adipocytes express aldosterone synthase (CYP11B2) and produce aldo. The mineralocorticoid receptor (MR), which is responsible for aldo signaling, is also found in these cells, but its role in regulating adipose tissue interactions with the vasculature is unknown. In this study, we investigated mechanisms whether MR activation in adipocytes regulates vascular reactivity. Conditional transgenic mice that overexpress MR in an adipocyte-specific manner were studied. Vascular reactivity of resistance mesenteric arteries to acetylcholine (Ach), sodium nitroprusside and phenylephrine (Phe), in the absence or presence of fat conditioned medium (Fcm) from control and adipocyte overexpressing MR (MROE) mice, was performed by myography. In basal conditions, endothelial dysfunction was not observed in MROE or control (Ctr) mice. However, exposure of arteries from control mice to Fcm from MROE mice induces endothelial dysfunction (Ach 10-6M: 77.5±9.6% no Fcm vs. 49.8±7.5% Fcm, p<0.05), an effect blocked by N-acetyl-cysteine (an antioxidant) (Ach 10-6M: 82.2±6.6%). Resistance arteries from MROE mice had decreased Phe-induced contraction, compared to control mice (Phe 10-5M: 2.7±0.2 mN/mm Ctr vs. 1.7±0.2 mN/mm MROE, p<0.05). Rho Kinase activity, which regulates vascular contraction, is decreased in arteries and adipo tissue from MROE (mesenteric arteries, Ctr: 100±16.2% vs. MROE: 31.1±6.1%, arbitrary units, p<0.01; adipose tissue, Ctr: 100±12.6% vs. MROE: 51.3±9.3%, arbitrary units, p<0.01). In conclusion, MR in adipocytes may play an important role in the regulation of vascular function, through redox-sensitive pathways and activation of Rho kinase. Our study identifies novel mechanisms linking vascular/adipose tissue biology and aldo/MR activation, which may be particularly important in vascular dysfunction associated with hypertension and hyperaldosteronism.

• Item Type: Articles
• Additional Information: American-Heart-Association High Blood Pressure Research Scientific Sessions, New Orleans, LA, USA, 11-14 Sept 2013.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jenkins, Mrs Carol and Montezano, Dr Augusto and Nguyen Dinh Cat, Dr Aurelie and Touyz, Professor Rhian
• Authors: Nguyen Dinh Cat, A., Callera, G. E., Antunes, T. T., Montezano, A. C., He, Y., Jenkins, C., Carter, A., Jaisser, F., and Touyz, R. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Hypertension
• Publisher: American Heart Association
• ISSN: 0194-911X
• ISSN (Online): 1524-4563