Objectives There is little information available regarding local vasomotor regulating processes in chronic heart failure. In this study, we tested the hypothesis that chronic heart failure impaired the endothelial function, and long term captopril treatment might reverse endothelial activity through tissue endothelin (ET) pathway.Methods Forty Spraque-Dawley rats were divided into 4 groups including 15 rats in each of the sham-operated with or without captopril-treated groups and 5 rats in each of large infarcted with or without captopril-treated groups.Results Concentration-response curves obtained in aortic rings without endothelium revealed no difference in nitroprusside-induced relaxation. With endothelium, rightward shifting was noted only in the untreated large infarct group during acetylcholine-induced relaxation. As compared to the non-treated group, plasma ET-1 concentrations were lower in the captopril-treated with or without large infarct groups. However, endothelin-like immunoreactivity in endothelial cells and cytoplasma of smooth muscle cells of the media of the aorta were lower only in the non-treated large infarct group.Conclusions Endothelial function was impaired in the chronic heart failure model. Coverting enzyme inhibitor might improve endothelial function through the Local endothelin pathway.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.