Ethnopharmacological relevance Senecio nutans Sch. Bip. (Compositae) is an endemic plant of South America, and is used in herbal medicine in Andean communities for treating acute mountain sickness. Currently, the direct effects of hydroalcoholic extract of S. nutans (HAE S. nutans) or its isolated compounds on the vascular system are not well described. The aim of this study was to determine the effects and mechanism of action of S. nutans on vascular function in healthy rats. Material and methods Seven compounds were isolated from the HAE S. nutans, and their structures were characterized using spectroscopic techniques as 1D and 2D NMR, and mass spectrometry. Vascular reactivity experiments were carried out in rat aorta. S. nutans-dependent vasodilation and phenylephrine-dependent contraction were measured in endothelium-intact and endothelium-denuded aortic rings of male rats. Results Seven pure compounds were isolate from HAE S. nutans, but two pure compounds showed significant vasodilation in rat aorta: 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone (compound E) and 5-acetyl-6-hydroxy-2-isopropenyl-2,3-dihydrobenzofurane (compound G). Although HAE S. nutans induced vasodilation in absence of endothelium, the vasodilation in intact aorta, via NO, was higher. HAE S. nutans reduced calcium-dependent contraction in endothelium-intact, but not in endothelium-denuded aortic rings. Conclusion HAE S. nutans and its isolated compounds caused vasodilation in rat aorta in absence of endothelium, suggesting its vasodilator properties is endothelium-dependent (NO) and or independent, and may involve a modulation of the calcium channels. This result is of clinical interest as potential therapy control of blood pressure.