Irbesartan normalises the deficiency in glomerular nephrin expression in amodel of diabetes and hypertension

Aims/hypothesis. The location of nephrin has been identified as the slit-di aphragm of the glomerular podocyte. Recent evidence suggests that nephrin c ould play a key role in the function of the glomerular filtration barrier a nd the development of proteinuria but its status in long-term diabetes is s till not understood. We studied-the expression of nephrin in a hypertensive model of diabetic nephropathy and investigated:the potential influence of angiotensin II blockade on nephrin gene and protein expression. Methods. Streptozotocin-diabetic spontaneously hypertensive rats were given either no treatment or the angiotensin II antagonist, irbesartan, at a dos e of 15 mg/kg per day by gavage for 32 weeks. Non-diabetic spontaneously hy pertensive rats were used as a control group. Realtime RT-PCR and immunohis tochemistry were used to assess and quantify gene and protein expression of nephrin. Results. Diabetic spontaneously hypertensive rats developed albuminuria and had a reduction in both gene and protein expression of nephrin when compar ed with control rats. Irbesartan treatment prevented the development of alb uminuria and completely abrogated the down regulation of nephrin in diabeti c rats. Conclusion/interpretation. Long-term diabetes in spontaneously hypertensive rats is associated with a reduction in both gene and protein expression of nephrin within the kidney. These changes in nephrin levels were completely prevented by angiotensin II antagonist treatment, suggesting a potential n ovel mechanism to explain the antiproteinuric effect of agents which interr upt the renin-angiotensin system.