The Effects And Significance Of Renal Cell Hyperplasia And Apoptosis About Treatment With Various Antihypertensive Drugs On Juvenile SHRs

Objective To investigate the effects of renal cell hyperplasia and apoptosis about treatment with various antihypertensive drugs on one-month-old spontaneously hypertensives rats (SHRs) and evaluate its significance.Methods 36 one-month-old SHRs (male,24;female,12) were used in the study and randomly divided into six groups,five of which were respectively handled with Propranolol (50 mg/kg/d),Nefidipine (35 mg/kg/d),Hnalapril (30 mg/kg/d),Hydrochlorothiazide (75 mg/kg/d),Valsatan (30 mg/kg/d),and the sixth group was untreated (control group). After all SHRs were received their respective treatment daily,by gastric gavage for six weeks,laparotomy was performed and the kidneys were removed. Renal cell apoptosis was then assessed by in situ dUTP biotin nick-end labeling method (TUNEL) and transmission electron microscope. We investigated the effects and dynamic changes of renal cell apoptotic indexes and renal ponderal indexes about treatment with various anti-hypertensive drugs on one-month-old SHRs.Results 1 . Renal ponderal indexes in Enalapril group (6.52+0.32 mg/g) and Valsatan group (6.39+0.27 mg/g) compared with control group (7.25+0.22 mg/g) decreased,respectively,(P<0.01). Renal ponderal indexes in Nefidipine group (6.73+0.21 mg/g) compared w7ith control group decrease (P<0.05). There was no statistical significance in renalponderal indexes in Propranolol group (7.09+0.32 mg/g) and Hydrochlorothiazide group (7.22+0.53 mg/g) compared with control group (P>0. 05).2. Renal apoptotic indexes in Propranolol group (49.02+5.1 7%),Enalapril group (56.47+9.08%),Nefidipine (51.08+9.59%) and Valsatan group (55.73+4.34%) compared with control group (35.19+4.05%) increased,respectively,(P<0.01). There was no statistical significance in renal apoptotic indexes in Hydrochlorothiazide group (37.23+ 1.95%) compared with control group (P>0.05).3. Glomerular apoptotic indexes in Enalapril group (35.13+8.73%),Nefidipine group (35.80+1 1.03%) and Valsatan group (34.20+4.26%) compared with control group (19. 13+1 .86%) increased, respectively,(P<0.01). There was no statistical significance in glomerular apoptotic indexes in Propranolol group (27.1 3+3.20%) and Hydrochlorothiazide group ( 1 9.80 +1 .96%) compared with control group (P>0.05).4. Renal tubular apoptotic indexes in Propranolol (21.88 + 3.57%),Enalapril group (21.33 +3.44%) and Valsatan group (21.53+1.86%) compared with control group (15.07 +2.48%) increased,respectively,(P<0.01). There was no statistical significance in renal tubular apoptotic indexes in Nefidipine group ( 15.28+2.03%) and Hydrochlorothiazide group ( 1 7.35 d. } .83%) compared with control group (P>0.05).5. There was a negative correlation between renal apoptotic indexes and renal ponderal indexes in juvenile SHRs (r=-0.496,P<0.01).6. The ultramicrostructural changes of renal cell apoptosis include cytoplasm compaction and segregation of nuclear chromatin into small sharply delineated electron dense masses that abut the nuclear envelope.Conclusion 1. Renal ponderal indexes of juvenile SHRs increase obviously before SHRs suffer from high blood pressure. There is asignificantly negative correlation between renal ponderal indexes and renal cell apoptotic indexes,which suggests that there is an imbalance between renal cell hyperplasia and apoptosis.2. Some kinds of antihypertensive drugs,for example,Enalapril,Valsatan,Netidipine and Propranolol,can improve the imbalance between renal cell hyperplasia and apoptosis in juvenile SHRs. The role is hypertension-independent. There may be an important value on protecting renal function because of early medication.3. Early medication of thiazidc diuretics can't protect renal function in juvenile SHRs.4. Renal ponderal indexes and apoptotic indexes can be considered as an important mark to evaluate the role of antihypertensive drugs and to observe the process of remodeling in renal tissue.