<p>Selenium is an essential trace element important for human health and its deficiency is typically compensated through dietary supplementation, including selenite (SeO₃²⁻). In biological systems, SeO₃²⁻ 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/SeO₃²⁻) 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/SeO₃²⁻ induced a pronounced hypotensive response, accompanied by reductions in heart rate and augmentation index. Furthermore, GSH/SeO₃²⁻ 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 (Se⁰) 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/SeO₃²⁻ interaction. The hypotensive effect of GSH/SeO₃²⁻ 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/SeO₃²⁻ was dependent on sympathetic nervous system activity.</p>