Melatonin protects vascular homeostasis by restoring PVAT redox balance in arterial hypertension.

Perivascular adipose tissue (PVAT) exerts vasoprotective role by releasing factors that modulate vascular tone. In arterial hypertension (AH), PVAT undergoes phenotypic alterations characterized by increased oxidative stress, inflammation, and loss of anticontractile function. Melatonin is a pleiotropic molecule with antioxidant and anti-inflammatory properties. This study investigated whether melatonin restores PVAT function and improves vascular reactivity in spontaneously hypertensive rats (SHR). Wistar and SHR rats were treated with vehicle or melatonin (5 mg/kg/day, orally) for 14 days. Vascular reactivity was assessed in aortic rings with and without PVAT in response to phenylephrine and acetylcholine. Reactive oxygen species (ROS) generation, hydrogen peroxide levels, nitric oxide (NO) bioavailability, expression and activity of antioxidant enzymes, and inflammatory cytokines were measured in PVAT. WT1 brown adipocytes were stimulated with angiotensin II in the presence or absence of melatonin to evaluate redox-related gene expression and oxidative stress markers. SHR PVAT exhibited loss of anticontractile function and impaired endothelium-dependent relaxation, associated with elevated ROS and hydrogen peroxide production, reduced NO levels, and increased NOX-1 expression. Catalase activity and NO bioavailability were decreased, whereas pro-inflammatory cytokines were upregulated. Melatonin treatment restored the anticontractile effect of PVAT, improved acetylcholine-induced relaxation, reduced oxidative stress, restored catalase activity, and preserved NO levels. In vitro, melatonin prevented angiotensin II-induced ROS generation, NOX-1 upregulation, and catalase downregulation in adipocytes. Melatonin restores PVAT function and vascular reactivity in AH by reducing oxidative stress, preserving antioxidant enzyme activity, and improving NO bioavailability. Melatonin shows potential to reverse PVAT dysfunction in AH.