Objectives In this study the change of signal transducer and activator of transcription 3 (Stat 3) and expression of c-myc in the developing of left ventricular hypertrophy (LVH) of Goldblatt rat, Two-kidney, one-clip (2K1C) renovascular hypertensive rats (RHR), was observed, and at the same time the relationship between the activation of Stat3 and protein expression of c-myc as well as the intervention of valsartan was examined. The ultimate is to investigate the role and mechanism of AT1—Stat3—c-myc in the developing of LVH.
Methods Two-kidney, one-clip (2K1C) renovascular hypertension was induced in 22 male Sprague-Dawley rats. The rats were randomised to untreated hypertension group (group H, n = 11), valsartan treatment group (group V, n = 11) which gorged valsartan 30 mg·Kg-1·d-1, At the same time, 11 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 Ang II 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 (124.93 ± 10.95 mmHg) group than H group (170.97 ± 13.09 mmHg) (P < 0.05), and there was no difference between V (124.93 ± 10.95 mmHg) group and C group (122.65 ± 11.35 mmHg) (P > 0.05), LVH could be observed in H group (LVMI 3.68 ± 0.59 mg/g), but not in V (LVMI 2.92 ± 0.39 mg/g ) and C group (LVMI 2.84 ± 0.4 mg/g) (P < 0.05), and LVMI was no significant difference in V group and C group. The levels of Ang II in LV of H group (8.10 ± 2.64 mg/g ) were much higher than V group (5.31 ± 1.90 mg/g) and C group (5.11 ± 1.54 mg/g) (P < 0.05), and there was no significant difference in V group and C group. Immunostained activation of Stat 3 and positive expression of c-myc in LV in group H were both higher than those in group V and C (P < 0.05), and there was no difference between V group and C group. In the LV of Goldblatt rat, activation of Stat 3 is positively related to expression of c-myc.
Conclusions In the development of left ventricular hypertrophy of Goldblatt rat, the activation of Stat 3 and expression of c-myc increases significantly which are correlated with Ang II. Angiotensin II receptor subtype 1 (AT1) antagonist valsartan not only decreased SBP but inhibited the activation of Stat 3 and even protein expression of c-myc and occurrence of LVH; all of which indicates that Stat 3- —c-myc has close relation with AT1 receptor. AT1—Stat 3—c-myc may participate in the development and progression of cardiac hypertrophy and is probably a new signal parthway of cardiac hypertrophy.