Effects Of Aldosterone On Renal Podocyte Injury And CD2AP Expression And Role Of Eplerenone In Spontaneously Hypertensive Rats

Objective:To observe the condition of podocyte damage and CD2AP expression and the effect of aldosterone and mineralocorticoid receptor antagnist on podocyte and CD2AP at the earlier stage of renal damage in spontaneously hypertensive rats.Methods:Twenty male SHRs were randomly seperated into two groups:treated group and untreated group which included ten rats respectively.Ten Wistar-Kyoto rats were used as control group.Treated group rats were feed with eplerenone(50 mg/kg per day)in 2ml filtered water.Untreated group rats and control group rats were feed with the same volume filtered water as treated group every day.Systolic blood pressure of caudal artery was measured by tail-cuff plethysmography.Plasma creatinine,plasma aldosterone,microalbuminuria,urine creatinine and renal tissue aldosterone were detected respectively.Half quantitative RT-PCR and Wester blotting were performed to evaluate the gene expression and protein synthesis of CD2AP respectively.Morphology of podocyte was detected by transmission electron microscope.Results:Systolic blood pressure of SHRs was at the same level both in treated group and untreated group,but there was obviously higher systolic blood pressure level than that of control group(P＜0.05).Untreated group rats presented higher microalbuminuria level than control group and untreated group(P＜0.05).Serum creatinine clearance of treated group was higher than that of control group and untreated group.Plasma aldosterone and renal tissue aldosterone of untreated group were higher than that of control group(P＜0.05).Transmission electron micrograph showed light proliferation of mesangial cell and matrix and fusion of podocyte both in treated group and untreated group.Cytolysosome of tubular epithelial cell increased moderately in untreated group.Telangiectasis,infiltration of monocytes and hyperplasia of collagen fiber in area of renal interstitium were also observed in untreated group.Gene expression and protein synthesis of CD2AP in untreated group were significantly depressed by contrast with control group and treated group(P＜0.05).CD2AP gene expression and protein expression had negative correlations with microalbumimuria.Their correlation coefficient r were -0.413(P＜0.05)and -0.519 (P＜0.01)repectively.CD2AP gene expression had negative correlations with plasma aldosterone and renal tissue aldosterone.Their correlation coefficient r were -0.572(P＜0.01)and -0.463(P＜0.01)repectively.CD2AP protein expression had negative correlations with plasma aldosterone and renal tissue aldosterone.Their correlation coefficient r were -0.552(P＜0.01)and -0.577(P＜0.01)repectively.Conclusions:Young SHRs have a high level of plasma and renal tissue aldosterone and podocyte injury is concerned with aldosterone.Plasma and renal tissue aldosterone diminishes CD2AP expression.Eplerenone reduces microalbuminuria and ameliorates podocyte injury,attenuating CD2AP expression in SHRs and the effect is independent of blood pressure reduction.