37 ROLE OF POTASSIUM ON RENAL PROTECTION IN DOCA/SALT MICE

Abstract

Objectives: Recent animal and human studies have demonstrated that potassium depletion or hypokalemia in the presence of mineralocorticoid excess and high sodium state contributes to the pathogenesis of hypertension, stroke, arrhythmias, chronic heart and kidney diseases in association with tissue oxidative stress, inflammation, remodeling and fibrosis. We have recently reported that implantation of deoxycorticosterone-acetate (DOCA) with high salt diet in one-renin gene mice induced hypokalemia, coronary fibrosis, cardiac hypertrophy and dysfunction in absence of hypertension. The pathological changes in the DOCA treated mice can be reversed by reducing salt intake. Whether dietary potassium supplementation reverses DOCA/salt induced hypokalemia and cardiac and renal damages are unknown and studied? Method and Results: DOCA/salt mice progressively developed renal hypertrophy and fibrosis, albuminuria, and high serum creatinine associated with increased renal mRNA expression of transforming growth factor, tumor necrosis factor alpha, plasminogen activator inhibitor-1, fibronectin, collagen types I and III etc in absence of hypertension. Even late correcting hypokalemia by potassium supplementation to the DOCA/salt mice can partially reverse cardiac and renal hypertrophy, fibrosis, albuminuria, renal dysfunction in association with the reduction of the expression of the above genes in the kidney. In conclusion, potassium administration can prevent and reverse proteinuria, cardiac and renal hypertrophy and fibrosis and dysfunction induced by excess of DOCA and salt and hypokalemia independently of blood pressure reduction. Conclusion: These data provide strong evidence to suggest that potassium supplementation in the food might convey cost-effective cardiovascular protection to hypertensive patients.