Glutathione/Selenite Interaction Products as Potent Vascular Smooth Muscle Tone Modulators with Antihypertensive Effects in Spontaneously Hypertensive Rats

Abstract Selenium is an essential trace element important for human health and its deficiency is typically compensated through dietary supplementation, including selenite (SeO 3 2− ). In biological systems, SeO 3 2− undergoes multistep reduction, generating selenium species with distinct oxidation states and redox properties. In this study, we investigated the cardiovascular effects of a glutathione/selenite mixture (GSH/SeO 3 2− ) in spontaneously hypertensive rats (SHRs). Arterial pulse waves were recorded using a pressure microcatheter and vascular tension in isolated arteries was assessed by isometric wire myography. Intravenous administration of GSH/SeO 3 2− induced a pronounced hypotensive response, accompanied by reductions in heart rate and augmentation index. Furthermore, GSH/SeO 3 2− elicited heterogeneous vasomotor responses across mesenteric, femoral, and aortic vascular beds. Marked vasorelaxation observed in the mesenteric artery, a representative resistance vessel, appeared to be associated with the formation of elemental selenium (Se 0 ) and was partially endothelium-independent. In contrast, aortic segments exhibited marked vasoconstriction. Notably, co-application of superoxide dismutase and catalase attenuated this response, suggesting that aortic segments are more sensitive to ROS generated during the GSH/SeO 3 2− interaction. The hypotensive effect of GSH/SeO 3 2− was preserved in SHRs pretreated with losartan and captopril, indicating additional antihypertensive efficacy beyond the pharmacological inhibition of renin-angiotensin-aldosterone system. Importantly, the hypotensive action of GSH/SeO 3 2− was dependent on sympathetic nervous system activity.