Renoprotection and Its Mechanism of Fasudil in Nitric Oxide Synthase-Deficient Hypertensive Rats

Abstract

To investigate whether fasudil can improve renal microcirculation and protect the kidney in N^G-nitro-l-arginine methyl ester (l-NAME)-induced hypertensive rats by inhibiting Rho/Rho associated coiled-coil containing protein kinase (ROCK) signal pathway. The nitric oxide-deficient hypertension was induced by l-NAME (60 mg/l·d) which was provided in drinking water for 8 weeks in Wistar rats. Then they were randomly divided into l-NAME and l-NAME + fasudil groups. Blood, urine, and left kidney samples were collected after fasudil intervention for 6 weeks. Renal artery blood flow, renal function markers in serum and urine, morphological changes of renal interlobular artery, and expression levels of related proteins were detected. Compared with normal control rats, the levels of serum creatinine (SCr) and blood urea nitrogen (BUN) increased while creatinine clearance (CCr) decreased in l-NAME rats. Fasudil treatment significantly decreased SCr and BUN, and increased CCr compared with l-NAME group. Compared with normal controls, the intima of renal interlobular artery increased, the lumen narrowed, the expression of ROCK-1, phosphorylated myosin phosphatase 1/myosin phosphatase 1 (p-MYPT1/MYPT1) increased while endothelial nitric oxide synthase (eNOS) protein levels decreased in l-NAME group (all P < 0.05). Fasudil treatment reduced intimal hyperplasia and lumen stenosis of renal interlobular artery, downregulated ROCK-1 and p-MYPT protein levels and upregulated eNOS expression in l-NAME rats (all P < 0.05). Fasudil treatment improves renal function and structure of renal interlobar artery in nitric oxide-deficient hypertensive rats induced by l-NAME.