Renal Protective Effects And Mechanisms Of A New β-blocker TJ0711on SHR

Objective To investigate the renal protective effects and the mechanisms of TJ0711(anovel vasodilatory β-blocker with a1:1ratio for the β1/α1blocking activities) againsthypertension induced renal injury on SHR.Methods Thirty five SHR (spontaneously hypertensive rats) were randomly divided intofive groups: control (saline,20mg/kg/day), carvedilol (carvedilol,20mg/kg/day), TJ071110(TJ0711,10mg/kg/day), TJ071120(TJ0711,20mg/kg/day) and TJ071140(TJ0711,40mg/kg/day). Tail artery systolic blood pressure before and after drug administration wasmonitored weekly. Serum samples,24h urine and kidneys tissue were collected. Renalfunction was evaluated by blood urea nitrogen (BUN), serum creatinine (Scr), Cystatin C,C-reactive protein (CRP),24h total urine protein and24h urine albumin. The pathologicalchanges of kidney damage were revealed by Periodic Acid-Schiff (PAS) staining andHematoxylin-Eosim (HE) staining. The location and expression of Hypoxia-InducibleFactor-1α (HIF-1α), Vasohibin-1, Hemo Oxygenase-1(HO-1) and Endothelial Nitric OxideSynthase (eNOS) of renal tissue was detected by immunohistochemistry and Western blot.The levels of TNF-α, IL-1β, IL-10and Adiponectin in serum were measured by ELISA. Results TJ0711possesses similar potency for control of blood pressure as that of carvedilol.Compared to the control group,24h urine protein and histopathological changes wereobviously attenuated in TJ071120group. Serum IL-1β, TNF-α levels were significantlylower (p <0.05), IL-10and adiponectin levels were markedly increased (p<0.05) in TJ071120group. Immunohistochemistry and Western blot showed medium does of TJ0711canup-regulated HIF-1α, eNOS and HO-1expression and down-regulated vasohibin-1expression (p<0.05).Conclusion TJ0711is more effective to protect SHR against hypertension induced renalinjury as compared with carvedilol. Its protective effect is related to enhancing eNOSexpression through suppressing inflammatory cytokine secretion and attenuatingVasohibin-1expression to prevent HIF-1α from signal-induced degradation by whichpromotes HO-1expression to protect SHR against oxidative stress.