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 approximately 100 microM) induced relaxation in aortic rings pre-contracted with norepinephrine (NE, 1 microM) or KCl (60 mM), with pEC(50) value 4.37+/-0.02 and 4.52+/-0.04. Pretreatment with pinocembrin (30 or 50 microM) also inhibited contractile responses to NE and KCl. The vasorelaxant effect of pinocembrin relied on intact endothelium partially, and incubation with n(omega)-nitro-l-arginine methyl ester (l-NAME, 100 microM) or methylene blue (10 microM) significantly inhibited the effect, however indomethacin (5 microM) had no influence on the action. In endothelium-denuded rings, the vasorelaxant effect of pinocembrin was reduced by glibenclamide (10 microM), tetraethylammonium (5 mM) and 4-aminopyridine (100 microM). Pinocembrin also reduced NE-induced transient contraction in Ca(2+)-free solution and inhibited contraction induced by increasing external calcium in Ca(2+)-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 Ca(2+) channels.