RENAL AND CARDIAC RENALASE EXPRESSION DURING NORMAL AND HIGH-SALT DIETS IN CHRONIC KIDNEY DISEASE RAT MODEL: 2D.06

Abstract

Renalase, a new regulator of cardiac function and blood pressure (BP), is a monoamine oxidase secreted into blood mainly by the kidney but also by the heart and other tissues. A reduced renalase expression was described in patients and in animal models of chronic kidney disease (CKD) and hypertension. In addition, the renalase knockout mouse is hypertensive and exquisitely sensitive to cardiac ischemia. The aim of the present study was to examine the influence of high sodium intake (HS) on renal and cardiac expression of renalase in rats submitted to 3/4 nephrectomy (3/4nx) and Sham surgery (Sham). Ten days after surgery, 3/4nx and Sham animals received a normal (NS) or a HS diet (40mmol/kg/day) during four days. BP and heart rate (HR) were measured daily using a photoelectric tail-cuff pulse detector. Fourteen days after surgery the animals were sacrificed and left ventricle (LV) and renal cortex (RC) were collected for protein quantification by Western-blotting using the anti-renalase polyclonal primary antibody (1:200, Abcam, UK). In addition, cardiac morphometry and transversal cardiomyocyte diameter (TCD) were also evaluated in all groups. BP, HR and TCD were significantly increased in 3/4nx rats throughout the study. In addition, HS diet significantly increased BP, HR and TCD in both 3/4nx and Sham rats. During NS diet the dimmer form of renalase was significantly reduced in both RC and LV from 3/4nx rats whereas during HS diet both monomer and dimmer renalase forms were reduced in both RC and LV from 3/4nx rats. Moreover, HS diet significantly decreased both monomer and dimmer renalase isoforms in the LV from 3/4nx rats when compared with NS intake. Our results show that the reduced renalase expression in the LV from 3/4nx rats is further accentuated during HS intake. It is suggested that this may contribute to the increased sodium-sensitivity of BP and enhanced cardiovascular risk in CKD.