Influence of Valsartan on myocardial apoptosis in spontaneously hypertensive rats.
OBJECTIVE
To explore the pathogenic changes of myocardial apoptosis in heart hypertrophy during hypertension and evaluate the anti-apoptosis effect of Valsartan.


METHODS
Thirty spontaneously hypertensive rats (SHRs) were divided into two groups: 15 treated with Valsartan (20 mg x kg(-1) x d(-1)) (SHR + Valsartan group), the others with placebo (SHR + placebo group), with 15 normal Wistar rats as control. Systolic blood pressure was measured by the tail-cuff method. The observation period was from 8 to 16 weeks of age. Cardiac apoptosis was evaluated by a Terminal Deoxynucleotidyl Transferase-Mediated dUTP-biotin Nick End Labeling (TUNEL) assay.


RESULTS
Mean blood pressure values were 127 +/- 2 mm Hg in controls, 163 +/- 6 mm Hg in the SHR + Valsartan group and 193 +/- 7 mm Hg in the SHR + placebo group at 16 weeks of age, whereas the blood pressure in 8-week-old SHR and Wistar rats were 175 +/- 3 mm Hg and 125 +/- 5 mm Hg, respectively. The ratio of the heart weight over body weight declined in Wistar (3.07 +/- 0.03 mg/g) and SHR + Valsartan groups (3.22 +/- 0.19 mg/g) compared with the SHR + placebo group (4.02 +/- 0.31 mg/g) (P < 0.05). The density of TUNEL-positive cells in Wistar and SHR +/- Valsartan groups was 23.3 +/- 3.3 nuclei/HPF and 35.0 +/- 1.3 nuclei/HPF, both of which were significantly less than that of the SHR + placebo group (116.7 +/- 11.3 nuclei/HPF).


CONCLUSIONS
In response to chronic pressure overload, cardiomyocyte-specific apoptosis contributes to the transition from compensatory hypertrophy to decompensation. Apoptosis may be effectively inhibited by Valsartan in the early stage of hypertension.
Li
Weimin
W
Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. wml@public.hr.hl.cn
Sun
Ningling
N
Liu
Wei
W
Chen
Yuanyuan
Y
Yu
Youzhi
Y
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006332:Cardiomegaly / Q000473:pathology; D006973:Hypertension / Q000473:pathology*; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000068756:Valsartan
D000959:Antihypertensive Agents; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine