Chronic Ang-(1-7) Or A779 Stz Induced Diabetic Rat Kidney Function

The renin-angiotensin system plays a critical role in blood pressure control and body fluid and electrolyte homeostasis.Besides angiotensin(Ang)Ⅱ,a number of new components have been discovered,such as angiotensin converting enzyme 2 (ACE2),renin receptor,Ang-(1-7) and Ang-(1-7) receptor Mas.These newly discovered RAS family members also play important biological activities.Ang-(1-7) has become an angiotensin of interest in the past few years.Evidence for the existence of ACE2 and Ang-(1-7) receptor Mas indicates a more comprehensive understanding of RAS.In the RAS,different components play different roles.AngⅡcontracts vessels and accelerates cell proliferation,while angiotensin(1-7) itself causes or enhances vasodilation and inhibits vascular contractions.On the other hand,AngⅡreceptor type 2(AT₂R) often counteracts the function induced by AngⅡreceptor type 1(AT₁R),simultaneously it relates to the function of Ang-(1-7) receptor Mas.In a word,the dual function of RAS can be concluded as the antagonism of AngⅡand Ang-(1-7),and the antagonism of AT₁R,AT₂R and Mas.As evidence indicates that the kidney regulates its function via a self-contained RAS in a paracrine fashion,the aim of the present study was to investigate the action of Ang(1-7) on the renal tissue RAS in STZ-induced diabetic rats.We also determined the effect of exogenous Ang-(1-7) and A779 on the expression of ACE, ACE2,AT₁R,AT2R,and MAS,as well as the expression of kidney TGF-β1.Four groups of rats were studied after 12-w treatment of streptozotocin(STZ):1) control group(C),2) STZ-induced diabetic group(D),3) STZ-induced diabetic rats with Ang(1-7) injection group(D+Ang1-7),and 4) STZ-induced diabetic rats with A779 injection group(D + A779).The results obtained indicated that the renal function of Ang(1-7)-treated rats was the worst among the three diabetic groups.By realtime PCR,Ang(1-7) treatment increased kidney ACE mRNA level.ACE2 expression decreased in Ang(1-7) group and increased in A779 rats,compared with that in the diabetic group.AT₁R expression increased in both Ang(1-7) and A779 groups,while the expression of both AT₂R and MAS receptors decreased.By using western blotting,kidney TGF-β1 protein expression increased significantly in both Ang(1-7) and A779 groups.In non-treated diabetic rats,the TGF-β1 protein expression had no significant difference from the control group.In summary,exogenous Ang(1-7) application can not ameliorate the renal injury in STZ-induced diabetic rats;on the contrary,it accelerates the progress of diabetic nephropathy.