TNF? Deficiency Improves Endothelial Function And Cardiovascular Injury In Salt-Sensitive Hypertension

ObjectiveTo investigate the role of tumor necrosis factor alpha?TNF??in endo thelial dysfunction and cardiac vascular damage in deoxycorticosterone ac etate?DOCA?salt-sensitive hypertension.MethodsC57BL/6 and TNF?^-/-mice were randomly divided into four group:normal control group,DOCA salt-sensitive hypertension group,and TNF?^-/-control group,TNF?^-/-DOCA salt-sensitive hypertension group.Hypertensive animal model was established by removal of one kidney plus DOCA and salt treatment.The systolic blood pressuer?SBP?was measured by tail-cuff method,acetylcholin-induced endothelium dependent relaxation?EDR?wasdetermined by organ chamber bath,Western blot was used for the measurement of related protein expression,DHE fluorescene staining was used for determination in site vascular oxygen free radical production.ResultsDOCA-salt treatment for 5 weeks significantly increased SBP,cardia and aortic hypertrophy and cardiac fibrosis,and impaired EDR.TNF?gen knockout significantly reduced cardiac and vascular hypertrophy and aortic ROS fluorescence intensity,impproved EDR with a mild reduction in SBP in DOCA-hypertensive mice.The protein expression of TNF?,TGF-?1,and fibronectin were significantly increased in the aorta of DOCA hypertensive mice.The TNF?gene knockout reversed the changes in these molecules mentioned above in DOCA-sensitive hypertensive mice.ConclusionsOur results suggest that TNF?play a very important role in vascular endothelial dysfunction and cardiovascular injuryin salt-sensitive hypertension.The underlying mechanism may involve increased oxygen free radical production andenhanced fibrosis process in cardiovascular system.Our results may provide important scientific evidence that TNF?as target moleculefor treatment of hypertension and endothelial cell dysfunction.