Effect of Infliximab versus Captopril on Deoxycorticosterone Acetate-Induced Hypertension in Rats

Background Hypertension is a primary risk factor for cardiovascular disease, the leading cause of global mortality. Inflammation, mediated by Tumor Necrosis Factor-α (TNF-α), is increasingly recognized as a key contributor to pathogenesis of hypertension. This study aimed to evaluate the antihypertensive and pleiotropic effects of TNF-α inhibitor (infliximab) compared with ACE inhibitor (captopril), either as a monotherapy or combined therapy, in a deoxycorticosterone acetate (DOCA)-salt-induced hypertension model in rats. Methods 72 male Wistar albino rats were divided into 6 groups:negative control,sham-operated, positive control DOCA-salt,DOCA+captopril, DOCA+infliximab,and DOCA+captopril+infliximab. Hypertension was induced over three weeks,followed by a three-week treatment period.We assessed serial blood pressure,plasma,and aortic biomarkers of endothelial function (NO, ET-1), inflammation (TNF-α, IL-6),oxidative stress (SOD, MDA),and renin-angiotensin system (Ang II). Lipid profiles,metabolic markers,and histopathological changes in heart and aorta were also analyzed. Results DOCA-salt model induced hypertension,dyslipidemia,inflammation,oxidative stress,and adverse cardiovascular remodeling.All treatment regimens significantly reduced blood pressure compared to positive control.Captopril monotherapy was more effective than infliximab monotherapy in reducing blood pressure.Combination of captopril and infliximab demonstrated the most profound and synergistic reduction in blood pressure and ameliorated nearly all pathological parameters. Combination therapy was superior in improving lipid profiles, normalizing vascular and inflammatory markers,reducing oxidative stress,and reversing structural changes in heart and aorta. Conclusion Both infliximab & captopril mitigate DOCA-salt-induced hypertension and its associated end-organ damage. The superior efficacy of the combination therapy suggests a synergistic interplay between RAAS inhibition and anti-inflammatory pathways.Targeting inflammation with agents like infliximab represents a promising therapeutic strategy,particularly as an adjunct to conventional antihypertensive treatments.