Role And Change Of Stat3 In The Left Ventricular Hypertrophy Of Hypertension

Objective: In this study the change of signal transducer and activator of transcription 3 (Stat3) in the developing of left ventricular hypertrophy(LVH) of renovascular hypertensive rats(RHR) was observed, and at the same time the relationship between the activation of Stat3 and systolic blood pressure, relative wall thickness, left ventricular concentration of angiotensinII (AngIIl) and protein expression of c-myc as well as the intervention of valsartan or spironolactone was examined. The ultimate is to investigate the role and mechanism of StatS in the developing of LVH.Methods: Two-kidney, one-clip(2K1C) renovascular hypertension was induced in fifty-six male Sprague-Dawley rats. The rats were randomized to untreated hypertension group (group H, n=ll), spironolactone treatment group(group S, n=12) which gorged spironolactone 50 mg Kg-1 d-1, valsartan treatment group (group V, n=ll) which gorged valsartan 30 mg Kg-1 d-1, spironolactone and valsartan combined treatment group (group S+V, n=l 1) which gorged spironolactone 50 mg Kg-1 d-1 and valsartan 30 mg Kg-1 d-1. At the same time, ten sham-operated rats served as control group (group C, n=10) which gorged water of equal volume. The tail cuff blood pressure was detected every week and echocardiogram was detected every other week. After eight weeks treatment, the rats were killed and the samples of the left ventricle were collected. The concentration of Angll in left ventricle was assessed by radioimmunoassay. Immunohistochemistry was adopted to exam the activation of Stat3 and protein expression of c-myc.Results: After eight weeks treatment, the blood pressure(BP) was lower in V, S+V, and C groups than S group and H group (P<0.05). LVH could be observed in H group and S group, but not in V, S+V and C group. The meridional end systolic stress (MESS) and relative wall thickness (RWT) were both higher in S group and H group than those in other three groups. While there was no significant difference in BP, MESS and RWTbetween H group and S group. Immunostained activation of Stat3 and positive expression of c-myc in LV in group H and group S were both higher than those in group V, S+V and C (P<0.05). The levels of AngII in LV of H group were much higher than the other four groups (P<0.05). In the LV of RHR, activation of Stat3 is positively related to BP, MESS and RWT. There was no relationship between activation of Stat3 and the concentration of Angn in LV. And activation of Stat3 was correlated with the protein expression of c-myc.Conclusion: In the development of left ventricular hypertrophy of RHR, the activation of Stat3 increases significantly, which doesn't completely depend on the regulation of AngII. Sustained pressure overload plays an important role in the activation of Stat3 which was correlated with MESS or RWT or protein expression of c-myc. Angiotensin n receptor subtype 1 (ATI) antagonist valsartan not only decreased SBP and MESS but inhibited the activation of Stat3 and even protein expression of c-myc and occurrence of LVH; while spironolactone had little effect on BP or MESS, and it also could't affect the RWT, activation of Stat3 and then the protein expression of c-myc, all of which indicates that StatS has close relation with ATI receptor. Stat3 may participate in the development and progression of cardiac hypertrophy and is probably a new activator of transcription in signal transduction of cardiac hypertrophy.