An ethyl acetate fraction obtained from a Southern Brazilian red wine relaxes rat mesenteric arterial bed through hyperpolarization and NO-cGMP pathway

Our results showed that after the tonus of MAB was increased with phenylephrine (PE), increasing concentrations of CE induced a concentration-dependent relaxation; moreover, EAF was more potent in relaxing the MAB when compared with CE. In vessels depolarized with KCl (80 mM) or treated with the Na+/K+-ATPase pump inhibitor, ouabain (OUA; 100 μM), or with the K+ channel blockers: barium (BaCl2, 100 μM) and tetraethylammonium (TEA; 500 μM ), the effect of EAF was significantly reduced. However, this effect was not altered by the ATP-dependent K+ (KATP) channel blocker, glibenclamide (GLI; 100 μM) as well as Charybdotoxin (ChTx 10 nM), a nonselective inhibitor of KCa channels of large and intermediate conductance plus Apamin (Apamin 100 nM), a specific inhibitor of KCa channels of small conductance. The residual vasodilator effect of EAF observed in vessels pretreated with L-NOARG (100 μM), 1H-[1,2,4,] oxadiazolo[4,3-alfa]quinoxalin, ODQ (10 μM) or KCl (80 mM), given separately, was reduced by the administration of KCl (40 mM) plus L-NOARG (100 μM). The present study demonstrates that the vasodilator effect of EAF is partially dependent upon membrane hyperpolarization in combination with nitric oxide (NO) release.