A new oxime synthesized from Senecio nutans SCh. Bip (chachacoma) reduces calcium influx in the vascular contractile response in rat aorta

Abstract

Senecio nutans Sch. Bip is an endemic plant commonly employed in the Andes culture to counteract the effects of mountain sickness, and its bioactive molecules could provide new drugs for treating hypertension. The purpose was to determine whether the vascular response of the plant bioactive molecules, such as (5-acetyl-6-hydroxy-2-isopropenyl-2,3-dihydrobenzofurane; Sn–I), could be improved by a simple structural modification to synthesize oximes (Ox–Sn–I). We characterized both compounds using IR and NMR spectroscopy and Heteronuclear Multiple Quantum Coherence (HMQC). We investigated vascular relaxation mechanisms in response to Sn–I and Ox–Sn–I using rat aorta and vascular smooth muscle cells (A7r5) as experimental models. Preincubation of aortic rings with Sn–I (10⁻⁵ M) significantly (p < 0.001) decreased the contractile effect in response to phenylephrine (PE) and potassium chloride (KCl). The sensitivity (EC₅₀) to PE significantly (p < 0.01) decreased in the presence of Sn–I (10⁻⁵ M), but not with Ox–Sn–I. Sn–I significantly (p < 0.001) reduced the PE-induced contraction under calcium-free conditions. When A7r5 cells were preincubated with Sn–I and Ox–Sn–I (10⁻⁵ M), both compounds blunted the increase in intracellular Ca²⁺ induced by KCl. 2,3-Dihydrobenzofurane derived from S. nutans (Sn–I) reduces the contractile response probably by blocking Ca²⁺ entry through voltage-gated Ca²⁺ channels (VGCC) in vascular smooth cells. This effect also causes relaxation in rat aorta mediated by reduction of intracellular Ca²⁺ concentration, rather than an increase of NO generation in endothelial vascular cells.