Endothelium-dependent and -independent relaxation induced by pinocembrin in rat aortic rings

The aim of present study was to evaluate the vasorelaxant effects of the flavonone pinocembrin and its possible mechanisms in isolated rat aortic rings. Pinocembrin (5 ∼ 100 μM) induced relaxation in aortic rings pre-contracted with norepinephrine (NE, 1 μM) or KCl (60 mM), with pEC50 value 4.37 ± 0.02 and 4.52 ± 0.04. Pretreatment with pinocembrin (30 or 50 μM) also inhibited contractile responses to NE and KCl. The vasorelaxant effect of pinocembrin relied on intact endothelium partially, and incubation with nω-nitro-l-arginine methyl ester (l-NAME, 100 μM) or methylene blue (10 μM) significantly inhibited the effect, however indomethacin (5 μM) had no influence on the action. In endothelium-denuded rings, the vasorelaxant effect of pinocembrin was reduced by glibenclamide (10 μM), tetraethylammonium (5 mM) and 4-aminopyridine (100 μM). Pinocembrin also reduced NE-induced transient contraction in Ca2+-free solution and inhibited contraction induced by increasing external calcium in Ca2+-free medium plus 60 mM KCl. Our results suggest that pinocembrin induces relaxation in rat aortic rings through an endothelium-dependent pathway, involving NO-cGMP, and also through an endothelium-independent pathway, opening K+ channels and blockade of Ca2+ channels.