Modulation way classical and alternatives of renin angiotensin system (ras) in mesangial cells after exposure to fructose.

Background: Our 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 (AngII) 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 AngIIof immortalized human mesangial cells (IMCH)exposed to low and high concentration of fructose. Methods: IMCH 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. Results: Among the AngIIforming enzymes, fructose decreased ACE activity in cell lysate.Both fructose concentrations increased chymase 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 increasedin culture medium.We did not detected differences in ACE2 activity. Conclusion: The results suggest fructose modulates renal and systemic RAS in IMCH acting in the classical andalternative pathways of AngII formation. Additionally this sugar was able to increase NEP activity, forming Ang-1-7. Quantitation of angiotensin remains necessary to better understand how the end effector is available in IMCH and evaluate possible effects on glomerular physiology.