Dioclein, a new nitric oxide- and endothelium-dependent vasodilator flavonoid

In the present work, the vasorelaxant effect of dioclein, a new flavonoid isolated from Dioclea grandiflora (Leguminoseae), was investigated in the rat aorta. Dioclein induced a concentration-dependent relaxation in vessels pre-contracted with phenylephrine (IC50 = 1.3 +/- 0.3 mu M), a response which was abolished after endothelium removal. Neither indomethacin (10 mu M), an inhibitor of cyclo-oxygenase, nor atropine (1 mu M), an antagonist of muscarinic receptors, modified the effect of dioclein. Dioclein (30 mu M) induced a significant increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in aortic rings with endothelium. The nitric oxide (NO) synthase inhibitor, N-G-nitro-L-arginine-methyl-ester (L-NAME, 300 mu M), strongly inhibited or abolished the relaxing effect and rise in cyclic GMP levels induced by dioclein. Furthermore, dioclein (30 mu M) had no effect on the endothelium-independent relaxation produced by the NO donor, 3-morpholino-sydnonimine (SIN-1), while superoxide dismutase (100 U ml(-1)) significantly potentiated it. These results indicate that, in the rat aorta, dioclein induces a NO- and endothelium-dependent vasorelaxant effect, which is associated with cyclic GMP elevation. This vasorelaxation likely results from enhanced synthesis of NO rather than enhanced biological activity of NO. (C) 1999 Elsevier Science B.V. All rights reserved.