Effect of Transient Prehypertensive Treatment with Losartan on Blood Pressure and Myocardium Fibrosis in Spontanous Hypertension Rats

Objective To explore the effects of transient prehypertensive treatment with losartan in spontaneously hypertensive rats(SHR)on blood pressure(BP)and myocardium fibrosis.Methods Four-week-old male SHRs were randomized to 3 groups:early treatment group [with 4-week-old rats administered with losartan 20 mg/(kg·d)for 4 weeks],adult treatment group(with 12-week-old rats treated with the same dose and duration of losartan),and SHR-control group(with distilled water delivered at the age of 4 weeks).Age-and-sex-matched normotensive rats(WKY)served as negative control(with distilled water fed at the age of 4 weeks),8 rats in each group.BP follow-up was performed via tail-culf for 24 weeks.Then heart-to-body ratio(H/B,the ratio of cardiac mass to body weight)and the left ventricular mass index(LVMI,the ratio of left ventricular mass to body weight)were analyzed in the decapitated rats.Myocardial collagen content was assessed with sirus-red staining.Plasma and myocardial angiotensin Ⅱ(Ang Ⅱ)levels were determined by radioimmunoassay.Results BP was decreased significantly in the early treatment group with rats aged 24 weeks was strikingly lower than SHR-controls,but the difference between the rats receiving early treatment and WKY ones was not significant.BP monitoring at the 16th week revealed significant reductions in adult losartan treatment group and surged at Week 20.There was no significant difference of BP between the adult treatment group and SHR-control at week 24.H/B,LVMI,and myocardial collagen content was obviously lower in the early treatment group than that in SHR-control group(P0.05),but no significant differences were found between the early treatment rats and the adult treatment ones(P0.05).Compared with the SHR-control,the early treatment group showed a remarkably declined Ang Ⅱ content in plasma and myocardium(P0.01),while the adult treatment group displayed slightly higher Ang Ⅱ level which was not significant in statistics(P0.05).Conclusion Transient prehypertensive treatment with losartan can delay the development of hypertension in SHR and can ameliorate myocardium fibrosis,the mechanism of which may be related with the inhibition of renin-angiotensin system activity.