MODULATION WAY CLASSICAL AND ALTERNATIVES OF RENIN ANGIOTENSIN SYSTEM (RAS) IN MESANGIAL CELLS AFTER EXPOSURE TO FRUCTOSE.

Abstract

BackgroundOur group demonstrated previously that rats subjected to a high fructose diet showed increased activity of kidney ACE. In order to understand the effect of fructose in the forming process of angiotensin II (Ang II) and angiotensin 1–7 (Ang1–7) affecting the levels of these effectors, the aim of this study was to evaluate the activities of the RAS enzymes responsible for the formation of Ang1–7 and Ang II of immortalized human mesangial cells (IMCH)exposed to low and high concentration of fructose.MethodsIMCH were divided into control (low glucose medium), Fructose 5 mM(medium + 5 mM Fructose) and Fructose 30mM(medium + 30 mM Fructose) groups. The enzymatic activity of ACE, chymase, cathepsin D, Neutral Endopeptidase (NEP) and ACE2 were evaluated using Z‐Phe‐His‐Leu, Abz‐AIKFFSAQ‐EDDnp, Abz‐AIAFFSRQ‐EDDnp, Abz(d)‐Arg‐Gly‐Leu, Mca‐APK (DNP) as substrates, respectively. Data were analyzed using ANOVA one way.ResultsAmong the AngII forming enzymes, fructose decreased ACE activity (CG:0,044±0,01 vs.F5:0,016±0,004* vs. F30:0,008±0,002* mU/mg protein) in cell lysate. Both fructose concentrations increased chymase (CG:0,85±0,03 vs. F5:1,07±0,07* vs. F30:0,99±0,05* nM/min/mL) in the culture medium. No effect was observed on the activity of cathepsin D. When evaluating the activities of peptidases forming Ang‐1–7, NEP activity was decreased in lysate cells in F30 group and decreased in F5 group in culture medium. We did not detect differences in ACE2 activity.ConclusionThe results suggest fructose modulates renal and systemic RAS in IMCH acting in the classical and alternative pathways of Ang II formation. Additionally, this sugar was able to decrease NEP activity, forming Ang‐1–7. Quantitation of angiotensin remains necessary to better understand how the end effector is available in IMCH and to evaluate possible effects on glomerular physiology.Support or Funding InformationCapesThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.