PS 13-16 MATRIX METALLOPROTEINASE-2 AND PLASMINOGEN ACTIVATOR INHIBITOR-1 MAY CONTRIBUTE TO DEOXYCORTICOSTERONE-ACETATE/SALT INDUCED RENAL LESION AND. (September 2016)

• Record Type: Journal Article
• Authors: Wang, Qing; Haefliger, Jacques-Antoine; Alonso, Florian
• Is Part Of: Journal of hypertension. Volume 34:(2016) Supplement 1
• Publication Date: 2016-09
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000501110.87373.60
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Animal and human studies have demonstrated that potassium depletion or hypokalemia in the presence of high mineralocorticoid and high salt state contributes to the pathogenesis of hypertension, stroke, ventricular arrhythmias, chronic heart and kidney diseases in association with tissue oxidative stress, endothelial dysfunction, inflammation and fibrosis. We have previously reported that administration of deoxycorticosterone-acetate (DOCA) together with salt loading to one-renin gene mice induces hypokalemia, cardiac and renal hypertrophy and fibrosis and dysfunction, and increases inflammation and fibrosis related gene expressions independently of blood pressure (BP). Potassium supplementation in food can prevent the DOCA/salt induced organ damage and the related gene over expressions. The aim of this study is to investigate the impact of renal proteins such as Matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor-1 (PAI-1), eNOS etc. in the development of DOCA/salt induced renal lesion and dietary potassium supplementation mediated protection. Design and Method: DOCA/salt model was generated in male C57BL/6J one-renin gene mice for 3 months. After 5 weeks of the DOCA/salt treatment, the mice received additional 0.4% KCl drink fluid for 6 weeks. Intra-arterial BP was measured in conscious mouse. Kidneys were removed, reduced to powder into liquid nitrogen, and stored at -80°C. MMP-2, PAI-1, osteopontin, collagen types I, renin, cox2, eNOS, etc. were analyzed by western blots. Results: Chronic DOCA/salt administration to C57BL/6J one-renin gene mice caused hypokalemia, renal hypertrophy and fibrosis in absence of hypertension, and increased in renal protein expressions of MMP2 and PAI-1 (p < 0.05, DOCS/salt vs. control). Dietary potassium supplementation reversed DOCA/salt induced renal lesion and over expression of renal MMP-2 and PAI-1 proteins (p < 0.05, DOCS/salt vs. DOCA/salt + potassium). Conclusions: The data provides a new clue for studying molecular mechanisms of salt induced organ damage and potassium mediated protection.