Effects of PDTC on ventricular hypertrophy and congestive heart failure in hypertensive rats / 天津医药

ABSTRACT

Objective To evaluate the inhibitory effects of NF-κB inhibitor pyrrolidine dithiocar-bamate (PDTC) on NF-kappa B activity and the serum inflammatory mediators in hypertensive-ventricular hypertrophy-congestive heart fail?ure rats. Methods The rat model of hypertension-cardiac hypertrophy-heart failure was made from 42 male Dahl salt sen?sitive rats. Rats were randomly divided into seven groups including group A (normal diet group), group B (high salt diet group), group C (NF-κB inhibition in early stage), group D (NF-κB inhibition in hypertensive stage), group E (NF-κB inhibi?tion in cardiac hypertrophy stage of week 12) and group G (NF-κB inhibition in heart failure stage). There were six rats for each group. Rats were administrated 8%high salt diet and injected PDTC 100 mg/(kg·d)intraperitoneally according to the prescribed time. Changes of blood pressure, left ventricular end diastolic interventricular septal thickness (IVSD), left ven?tricular end diastolic posterior wall thickness (LVPWD), left ventricular end diastolic diameter (LVEDD), systolic left ventric?ular end diastolic diameter (LVESD), left ventricular ejection fraction (LVEF), heart, lung weight/ body weight ratio, NF-kappa B activity, tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1 and C-reactive protein (CRP) were observed in different treatment time points of PDCT. Results Levels of NF-κB and proinflammatory cy?tokines were reduced after early administration of PDTC, and the cardiac function was also decreased. The longer the treat?ment time, the greater the protective effect on heart. PDTC can effectively control blood pressure, and block left ventricular hypertrophy and left ventricular failure in a certain extent. The effects of PDTC were limited after persistent hypertension, and myocardial hypertrophy formation accompanied by heart failure. Conclusion PDTC plays a role in prevention and treatment of hypertension, left ventricular hypertrophy and congestive heart failure in model rats. Early application of PDTC could obviously maintain the normal cardiac function in rats with heart disease.