Abstract:

The vascular effects of 7-epiclusianone on the rat aorta were investigated. In the rat aortic rings with functional endothelia, 7-epiclusianone up to 10 μM induced a concentration-dependent vasodilatation of the sustained contractions induced by phenylephrine (0.3 μM). At concentrations higher than 10 μM, 7-epiclusianone induced a concentration-dependent contraction in the aortic rings. The vasodilator effect of 7-epiclusianone was drastically decreased with L-NAME (100 μM) as well as in endothelium-denuded aortic rings. Moreover, indomethacin (10 μM) induced a significant shift to the left in the vasodilator but did not modify the vasoconstrictor effect of 7-epiclusianone. In arteries without pre-contraction, 7-epiclusianone (3–100 μM) induced concentration-dependent contraction only in endothelium-intact and in the presence of L-NAME (100 μM). This effect was inhibited by indomethacin (10 μM) and ZM230487 (1 μM), selective inhibitors of cyclooxygenase and of 5-lipoxygenase, respectively. We can conclude that at low concentrations 7-epiclusianone induces an endothelium-dependent vasodilator effect in rat aortic rings. At higher concentrations and in conditions where NO synthase was inhibited, 7-epiclusianone induces a vasocontractile effect. Nitric oxide seems to participate in the vasodilatation, while endothelial cyclooxygenase- and 5-lipoxygenase-derived products play a role in the vasoconstrictor effect.