Beneficial effects of the Rho kinase inhibitor Y27632 in murine puromycin aminonucleoside nephrosis.

Journal Article (Journal Article)

BACKGROUND AND AIMS: Rho kinase (ROCK) inhibition reduces systemic blood pressure (BP) and decreases renal damage in animal models of kidney disease. The aim of this study was to determine if ROCK inhibition might have beneficial effects in glomerular disease processes that are independent of systemic BP. METHODS: We investigated the effects of the ROCK inhibitor Y27632 and hydralazine in murine puromycin aminonucleoside (PAN) nephrosis. RESULTS: Treatment with either Y27632 or hydralazine similarly reduced systolic BP compared to vehicle-treated controls. Seven days after treatment with PAN, albuminuria, proteinuria and effacement of podocyte foot processes were significantly reduced in Y27632- and hydralazine-treated mice compared to vehicle-treated animals. Treatment with PAN significantly reduced expression of the podocyte proteins nephrin and Neph1, and the loss of glomerular nephrin was attenuated by treatment with Y27632 but not by treatment with hydralazine. In cultured podocytes, PAN potently activated both Rho and ROCK, and PAN-induced ROCK activation was prevented by Y27632. CONCLUSIONS: The ROCK inhibitor Y27632 attenuated glomerular nephrin loss in murine PAN nephrosis independent of its effects on systemic BP.

Full Text

Duke Authors

Cited Authors

  • Wang, L; Ellis, MJ; Fields, TA; Howell, DN; Spurney, RF

Published Date

  • 2008

Published In

Volume / Issue

  • 31 / 2

Start / End Page

  • 111 - 121

PubMed ID

  • 18367845

Pubmed Central ID

  • PMC2821439

Electronic International Standard Serial Number (EISSN)

  • 1423-0143

Digital Object Identifier (DOI)

  • 10.1159/000121531


  • eng

Conference Location

  • Switzerland