Rivaroxaban attenuates the cardiovascular PAR1-related inflammation, fibrosis and atherogenicity in experimental hypertensive/ hypercholesterolemia rat model

Background: Hypertension and hypercholesterolemia serve as a predisposing component for cardiovascular disorders. Rivaroxaban, an oral anticoagulant used to preclude and treat venous thrombosis, atrial fibrillation and coronary artery syndrome. Objectives: The study aimed to highlight the potential cardiovascular protective effects of rivaroxaban on rats with high cholesterol/salt/fludrocortisone-induced hypertension.Methods: Male albino rats Wister strain were comprising four groups (eight rats/each): control, rivaroxaban (10mg/kg orally), FSC, and rivaroxaban+ FSC. The last two groups were subjected to oral FSC administration (Fludrocortisone 100μg/kg, NaCl 1% and Cholesterol 1%) for 21 days to explore the levels of systolic and diastolicblood pressure (SBP, DBP), electrocardiogram, cardiac contractility, body weight, serum sodium, lipids and glucose. The study assessed the cardiac inflammatory, protease-activated receptor1 (PAR1) by enzyme-linkedimmunoreactivity assay, and the histopathology of cardiac and aortic tissues α-smooth muscle actin(αSMA) with aortic endothelial nitric oxide synthase (eNOS) immunostain. Results: The FSC-treated rats demonstrated significant decreased contractility, increased SBP, DBP, MBP, serum sodium, lipids, and PAR1 levels. The results also revealedover expressed αSMA with decreased eNOS activity, degenerative alterations, inflammatory cells infiltration, and atheromatous formation; indicating development of hypertension/hypercholesterolemia. Rivaroxaban significantly improved all measurements with increased cardiac contractility and insignificant changes in electrocardiographreadings.Conclusion: Rivaroxaban exhibited a cardiovascular protective effect on the FSC-treated rats, primarily by ameliorating the hemodynamics, sodium, glucose, and lipids. Moreover, the drug demonstrated anti- inflammatory/antioxidant/antifibrotic effects, evidenced by the ameliorated PAR1, eNOS, and αSMA activity concurrently with antiatherogenic properties. Such effects endorse rivaroxaban benefits in treatment of hypertensive/hypercholesterolemic patients beyond its anticoagulation.