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 (IC(50)=1.3+/-0.3 microM), a response which was abolished after endothelium removal. Neither indomethacin (10 microM), an inhibitor of cyclo-oxygenase, nor atropine (1 microM), an antagonist of muscarinic receptors, modified the effect of dioclein. Dioclein (30 microM) 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 microM), strongly inhibited or abolished the relaxing effect and rise in cyclic GMP levels induced by dioclein. Furthermore, dioclein (30 microM) 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.
Lemos
V S
VS
Laboratório de Hipertensão, Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, Brazil.
Freitas
M R
MR
Muller
B
B
Lino
Y D
YD
Queiroga
C E
CE
Côrtes
S F
SF
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001938:Brazil; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D044950:Flavanones; D005419:Flavonoids; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C094747:dioclein; D010656:Phenylephrine; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D006152:Cyclic GMP