Vasorelaxant and antihypertensive activities of citroflavonoids (Hesperidin/Naringenin Mixture): Potential prophylactic of cardiovascular endothelial dysfunction

Background: Flavonoids in the Citrus genus have a positive influence in cardiometabolic parameters, preventing cardiovascular diseases (CVDs). The main flavonoids in sweet orange are hesperidin and naringenin. Objective: The aim of this study is to evaluate the cardiovascular effects of mixture of Hesperidin: Naringenin (mix-H:N). Materials and Methods: The relaxant effect and the mechanism of action of mix-H:N were studied on isolated aorta of Wistar rats. Aortic reactivity was determined through concentration-response curves of norepinephrine (NE) and carbamylcholine or carbachol (CCh) after intragastric administration of mix-H:N (150 mg/kg) for 30 days. The antihypertensive effect of a single dose of mix-H:N was studied on spontaneously hypertensive rats (SHR). Results: Mix-H:N produced concentration-dependent relaxation response in Wistar rat's aorta pre-contracted by NE. Inhibitors of NO production and inhibition of extracellular Ca2+ influx caused a significant blockade on the relaxation response to mix-H:N; besides, mix-H:N elicited a vasorelaxant effect on KCl (80 mM)-induced contraction. In addition, oral administration of 150 mg/kg of mix-H:N of SHR rats evoked a significant decrease in systolic and diastolic blood pressure at 5 h and 7 h after administration. Finally, sub-chronic oral administration of mix H:N for 30 days caused ex vivo vascular reactivity modification on NE-induced contraction and CCh-induced relaxation, improving endothelial function. Conclusion: The mix-H:N has the vasorelaxant and antihypertensive effect that may be attributed to an increase of NO production and a blockade of the Ca2+ channels on VSMCs. Furthermore, mix-H:N improves endothelial function of Wistar rats acting as a potential prophylactic against CVDs.