Pyrrolidine Dithiocarbamate (PDTC) Attenuates Heart Failure In Rats Though Reducing NADPH Oxidase Subunit P22^phox

Objective:This study is to investigate whether pyrrolidine dithiocarbamate(PDTC),a nuclear transcription factor NF-kB antagonist,also an antioxidants,can attenuate heart failure in rats through reducing NADPH oxidase subunit p22.Methods:60 adult male Sprague-Dawley rats weighing(250-300) g(provided by Animal Unit of Shanxi Medical University) were randomly divided into two groups:heart failure group(n=36) and the sham group(n= 24).In heart failure group,rats' left anterior descending coronary artery (LAD) was ligated to establish the heart failure model;while in the latter,rats' left anterior descending artery(LAD) was only exposed without ligation.Then heart failure group and the sham group randomly divided into 2 groups again:PDTC group and control group,PDTC group rats were treated with PDTC(150mg/kg/day) in drinking water for 4 weeks,while control group given normal drinking water.4 weeks later,cardiac function was reflected by hemodynamic measurement,and the levels of p22phox were examined by immunohistochemistry.The renal sympathetic nerve activity was also recorded.Results:1,Hemodynamics measurements:Our results revealed left ventricle function of HF rats was damaged,characterized as lower LVEDP,higher LV+dp/dt_max and LV-dp/dt_max compared with Sham rats.HF rats treated with PDTC had lower LVEDP levels,higher LV+dp/dtmax and LV-dp/dtmax levels compared with vehicle treated HF rats.2,Immunohistochemistry results:Compared with Sham groups,HF rats had more P22phox positive cell in heart and kidney.3,Effects of PDTC on sympathetic nerve activity of each group rats:Enhanced sympathetic nerve activity is one of the characteristics of heart failure.Renal sympathetic neuronal activity recording shows that HF rats produced a sympathoexcitatory response characterized by significant increases from baseline in RSNA.PDTC can attenuate sympathetic nerve activity in HF rats,but have no effect on sympathetic nerve activity in Sham rats. 4,malondialdehyde(MDA) Determination:MDA content increased in heart failure group(p <0.01).MDA level of the intervention group and the sham-operated group showed no significant difference(p> 0.05).5,RV/BW ratio and Lung/BW ratio of each group rats Our results revealed increased RY7BW ratio and Lung/BW ratio in HF rats.This indicated hypertrophy in right ventricle and pulmonary venous pleonaemia.Conclusion:The use of PDTC,which can inhibit the nuclear transcription factor NF-κB activity,reduces the NADPH oxidase subunit p22phox's expression in heart and kidney tissues of rats with ischemia-induced heart failure.