Copper overload induces oxidative stress in mesenteric PVAT and modulates vascular reactivity

Abstract Copper is an essential micronutrient involved in several physiological function; however, elevated copper levels are associated with vascular dysfunction. Previous evidence indi-cates that copper overload promotes inflammation in perivascular adipose tissue (PVAT), a key regulator of vascular function. In this context, we investigated whether chronic copper overload modulates the redox profile of mesenteric PVAT and vascular reactivity. Male Wistar rats, 8 weeks old, were divided into two groups: Control (saline, i.p.) and Copper (25.72 µg/kg/day of Cu, i.p., for 30 days). Mesenteric PVAT was collected for analysis of re-active oxygen species (ROS) production, nitric oxide (NO) bioavailability, H₂O₂ levels, total SOD activity, eNOS gene expression, and SOD1, catalase, and NOX4 protein expression. Vascular reactivity to phenylephrine was also evaluated. Serum samples were used for bio-chemical analyses. Chronic copper overload increased the fluorescent signal associated with ROS production in mesenteric PVAT, accompanied by reduced SOD1 protein expres-sion and increased NOX4 protein expression. No significant differences were observed in total SOD activity, eNOS gene expression, or catalase protein levels. NO bioavailability and H₂O₂ levels also remained unchanged. In mesenteric artery rings, copper treatment reduced vascular responsiveness to phenylephrine in the absence of PVAT, while the anticontractile effect of PVAT was maintained after copper exposure. Alterations in redox-related parame-ters were observed in mesenteric PVAT of Wistar rats that received copper, along with a re-duction in phenylephrine-induced contractile responses in mesenteric arteries in the ab-sence of PVAT. However, this reduced vasoconstrictor response was not observed in the presence of PVAT.