J Biomed 2017; 2:57-63. doi:10.7150/jbm.18881
Candesartan suppresses proteinuria and decrease of nephrin expression but hydralazine does not in hypertensive nephropathy
1. Department of Pharmacology, Faculty of Medicine, Kindai University, Osaka, Japan;
2. Department of Pathology, Faculty of Medicine, Kindai University, Osaka, Japan;
3. Life Science Institute, Kindai University, Osaka, Japan.
Kato T, Mizuguchi N, Ito A. Candesartan suppresses proteinuria and decrease of nephrin expression but hydralazine does not in hypertensive nephropathy. J Biomed 2017; 2:57-63. doi:10.7150/jbm.18881. Available from http://www.jbiomed.com/v02p0057.htm
Proteinuria is considered as an indicator of glomerular podocyte injuries and a major cause of chronic kidney disease. Podocytes include important and functional proteins including nephrin. We previously reported proteinuria and nephrin loss in the podocytes of malignant stroke-prone spontaneous hypertensive rats (MSHRSPs), a hypertensive nephropathy model. At first, we actually confirmed that the nephrin was reduced in the human glomeruli with diabetic nephropathy by immunohistochemistry. These specimens showed the tendency of increased blood pressure. Moreover, to investigate the molecular mechanisms of proteinuria and podocyte injuries, we examined the effects of a vasodilator, hydralazine, and an angiotensin receptor blocker, candesartan hydrochloride on the proteinuria and nephrin expression in MSHRSPs. As results, hydralazine had preventive effects on tubular injuries and renal dysfunction but not on podocyte injuries because hydralazine-treated MSHR developed proteinuria and exhibited nephrin loss from the glomeruli. However, candesartan plays protective functions against proteinuria and the decrease of nephrin in addition to the tubular injuries. Thus, candesartan could significantly suppress podocyte injuries. We conclude that podocyte injuries and proteinuria were dependent on an excessive angiotensin system, not mechanical stress.
Keywords: angiotensin receptor blocker, diabetic nephropathy, hypertensive nephropathy, nephrin, podocyte, vasodilator.