Novel insights into the physiology of renalase and its role in hypertension and heart disease

Renalase is an amine oxidase expressed in kidney, heart, liver, and brain that metabolizes catecholamines. Tissue and plasma levels are decreased in models of hypertension and chronic kidney disease. Its expression is modulated by salt intake, and urinary renalase may regulate catecholamines levels and effect renal sodium and phosphate transport. The renalase knockout mouse is hypertensive in the absence of significant changes in renal function. Sympathetic tone is increased as evidenced by elevated plasma and urine catecholamines. Studies in humans with resistant hypertension indicate that plasma renalase levels are inversely associated with systolic blood pressure. Additionally, a functional mutation in renalase (Glu37Asp), known to be associated with essential hypertension, also predicts more severe cardiac hypertrophy and dysfunction. Lastly, a single dose of recombinant renalase administered subcutaneously to rats with chronic kidney disease or to Spontaneously Hypertensive Stroke Prone rats significantly decreases blood pressure for more than 24 h. Available data suggest that renalase deficiency is associated with increased sympathetic tone and resistant hypertension, and recombinant renalase is a potent antihypertensive agent that may provide a valuable option for treating hypertension in chronic kidney disease.