Effect Of The Inhibition Of NF-κ B On Left Ventricular Hypertrophy In Goldblatt Rats

Objective: Left ventricular hypertrophy (LVH) is one of the main target organ damage in hypertension. LVH results in the reduction of cardiac systolic and diastolic function, and finally leads to heart failure. Up to now, we have studied the effects of the mechanical overload and hormone factors on LVH in hypertension. Currently, more and more researches focus on the molecular mechanisms of LVH. LVH is accepted to be the co-effects of the expression of the proliferation,hypertrophy and apoptosis genes, which are regulated by NF-κB, a key nuclear transcription and regulation factor. We hypothesize that NF-κB contributes to LVH in hypertension. To test this hypothesis, we examine the effect of PDTC(pyrrolidine dithiocarbamate), the inhibitor of NF-κB, on the expression of NF-κB,myocardial hypertrophy and fibrosis in the left ventricle in Goldblatt rats. Methods: The Goldblatt model of renovascular hypertension was made in twenty-one male Sprague-Dawley rats. The rats were randomized to non-intervention hypertension group (H group) and hypertension treated with PDTC group (P group). Ten Sham-operated rats served as control group (C group). P group were injected PDTC 100mg?kg-1?d-1 by S.C, as H group and C group were injected the same dosage of saline. The tail cuff blood pressure was measured every week and echocardiography was performed before operation and before death in each group. After 6 weeks of treatment, all the rats were killed and myocardial tissues were collected. Immunohistochemistry was adopted to examine the expression of NF-κB in the left ventricle. Interstitial collagen volume fraction (CVF) and perivascular collagen area (PVCA) were assessed by computer-assisted morphometry on the left ventricule sections stained with Victoria blue'B and ponceau. Results: PDTC significantly decreased SBP after 6 weeks' treatment. LVMI,LVPWD, IVSD,CVF and PVCA were all lower in P group than in H group(p<0.01), but these indexes in P group were still higher than in C group(p<0.05). We detected positive immunoreactivity of NF-κB in the nuclei of myocytes in H group. The expression of NF-κB in H group was more considerable than in C group and P group, and the expression of NF-κB in P group was still higher than in C group. Positive correlation was found between the expression of NF-κB and blood pressure,LVMI,IVSD,LVPWD after 6 weeks' treatment. Conclusions: (1) NF-κB contributes to the formation of LVH of hypertension. (2) NF-κB contributes to the formation of myocardial fibrosis. (3) NF-κB mediating inflammation mechanism might play some roles in the initiation and development of hypertension. (4) PDTC can not only suppress the expression of NF-κB, but also can significantly decrease blood pressure,partially reverse LVH and prevent myocardial fibrosis.