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

Introduction: 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).Methods: 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 (PE) and acetylcholine (ACh). Reactive oxygen species (ROS) generation, hydrogen peroxide (H 2 O 2 ) levels, nitric oxide (NO) bioavailability, expression and activity of antioxidant enzymes, and inflammatory cytokines were measured in PVAT. Results: In the analysis of vascular function, removal of PVAT from the aortic rings of Wistar rats significantly increased PE-induced contraction Emax, (% KCl); absence PVAT 196.5 ± 9.7 vs. presence PVAT 127.6 ± 4.8*. In contrast, PVAT removal had no effect on PE-induced contraction in aortic rings of SHR rats Emax, (% KCl); absence PVAT 204.7 ± 9.4 vs. presence PVAT 189.1 ± 9.8. Endothelium-dependent relaxation in response to ACh was not affected by the presence or absence of PVAT in aortas of Wistar rats. However, in SHR rats, the presence of PVAT reduced ACh-induced relaxation Emax, (% Relaxation); absence PVAT 78.01 ± 1.9 vs. presence PVAT 62.63 ± 3.0*. In contrast, in SHR rats, melatonin treatment restored the anticontractile effect of PVAT. Furthermore, in Wistar rats, melatonin did not alter ACh-induced endothelium-dependent relaxation in aortic rings with or without PVAT. However, in SHR rats, melatonin improved ACh-induced relaxation. SHR rats showed increased NOX-1 expression in PVAT, as well as increased ROS generation and H 2 O 2 production. Melatonin treatment attenuated these alterations. Furthermore, the antioxidant system in PVAT was evaluated. In SHR rats, a reduction in catalase activity in PVAT was observed, an alteration that was reversed by melatonin treatment. To investigate the contribution of NOX-1-derived ROS to PVAT dysfunction in HA, vascular reactivity assays were performed after incubation with ML171, a selective NOX-1 inhibitor. In SHR rats, ML171 restored the anticontractile properties of PVAT and significantly improved acetylcholine-mediated relaxation. HA reduced nitrite concentrations and NO levels in PVAT, effects that were reversed by melatonin treatment. AH significantly increased the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in PVAT. Treatment with melatonin attenuated these inflammatory responses, restoring the levels of these cytokines to values similar to those observed in normotensive controls.Conclusion: 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. Financial support: FAPEG - Foundation for Research Support of the State of Goiás This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.