{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T21:13:07Z","timestamp":1768770787689,"version":"3.49.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,2,22]],"date-time":"2011-02-22T00:00:00Z","timestamp":1298332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:p><jats:bold>BACKGROUND<\/jats:bold> It is well established that the pathogenesis of diabetic nephropathy is associated with abnormalities of renal nitric oxide (NO) generation. Many of the biological actions of NO are mediated by cGMP, which is rapidly degraded by phosphodiesterases. In this study, we evaluated the renoprotective effects of sildenafil (SIL), an inhibitor of phosphodiesterase\u20105, in type 2 diabetic rats.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold> Male Otsuka Long\u2010Evans Tokushima Fatty (OLETF) rats, a non\u2010insulin\u2010dependent diabetes model, and Long\u2010Evans Tokushima Otsuka rats, a non\u2010diabetic control, were treated with either SIL (2.5\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup> in drinking water) or undosed water for 28 weeks, starting at 30 weeks of age.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold> Sildenafil treatment significantly decreased albuminuria, attenuated glomerular hyperfiltration and resulted in a decrease in glomerular hypertrophy, in addition to a reduced glomerulosclerosis score and a dramatic decrease in the number of glomerular and tubulointerstitial proliferating cell nuclear antigen\u2010positive cells in OLETF rats. This was accompanied by a significant reduction in renal cortical mRNA levels of collagen types I and III. The increased mRNA levels of matrix metalloproteinase (MMP)\u20102, MMP\u20109, tissue inhibitors of MMPs (TIMP)\u20101 and TIMP\u20102 in the OLETF rats were significantly or partially attenuated by SIL treatment.<\/jats:p><jats:p><jats:bold>CONCLUSIONS<\/jats:bold> This study suggests that SIL attenuated diabetic nephropathy due to its potent antiproliferative effects and its regulatory effects on extracellular matrix. This latter effect is thought to be a result of its ability to affect the balance between MMPs and their inhibitors.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2010.01149.x","type":"journal-article","created":{"date-parts":[[2010,12,6]],"date-time":"2010-12-06T11:43:48Z","timestamp":1291635828000},"page":"1389-1400","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Sildenafil, a phosphodiesterase type 5 inhibitor, attenuates diabetic nephropathy in non\u2010insulin\u2010dependent Otsuka Long\u2010Evans Tokushima Fatty 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