The Influence Of Antihypertensive Drugs On Vascular Smooth Cell Apoptosis And Proliferation In Juvenile Spontaneously Hypertensive Rats

Objective: To observe the influence of different types antihypertensive drugs on aortic vascular smooth muscle cells (VSMC) proliferation and apoptosis, to investigate the mechanisms of preventive therapy to improve the disequilibrium of VSMC proliferation and apoptosis and the role and meaning of aortic vascular remodeling in earlier period of hypertension in Juvenile Spontaneously Hypertensive Rats.Methods: 36 spontaneously hypertensive rats (SHR), aging 4 weeks (24 male and 12 female) were divided into 6 groups randomly. One group served as control, five other groups were treated 6 weeks by Propranolol (50mg/kg.d),Enalapril(30mg/kg.d),Nefidipine(35mg/kg.d),Valsartan(30m g/kg.d), Hydroclorothiazide (75mg/kg.d) respectively. VSMC apoptosis was assessed by in situ TdT-mediated dUPT nick end labeling (TUNEL). Semi-quantitative analysis was used to calculate aortic VSMC apoptosis index (VSMCAI). Protein Bcl-2 and Bax were tested by immunohisto chemical method. Histologic study of the aorta was examined using light microscope.Results: 1. VSMCAI in Enalapril, Nefidipine and Valsartan groups was notably increased compared with control group while there were no significant differences between Propranolol and control, or Hydroclorothiazide and control.2. Bcl-2 protein in Enalapril and Valsartan groups was markedly decreased compared with in control group, and there were no significant difference between Propranolol and control or Hydroclorothiazide andcontrol.3. Bax protein in Valsartan group was markedly increased compared with control. There were no significant differences in other four groups compared with the control group.4. Bcl-2/Bax ratio was lowered notably in Enalapril, Nefidipine, Valsartan VS in control, while Propranolol, Hydroclorothiazide compared with control, there were no differences.5. Light microscope feature of VSMC apoptosis nucleus well-arranged, tunica intima smooth were discovered easily in Enalapril, Nefidipine,Valsartan groups. The microstructural changes,such as nucleus derangement, tunica intima Asper, collagen fibers proliferation, SMC hypertrophy were examined easily in Propranolol, Hydroclorothiazide and control groups.Conclusion: 1. There exists the disequilibrium of VSMC proliferation and apoptosis. Different type antihypertensive drugs had different influences on VSMCAI, which indicats the mechanisms of vascular remodeling affected by different types of antihypertensive drugs were not the same in juvenile spontaneously hypertensive Rats.2. Early antihypertensive treatment in juvenile SHR could affect vascular remodeling, which mediate the balance of VSMC proliferation and apoptosis.