title: Puerarin, an isoflavonoid derived from Radix puerariae, potentiates endothelium-independent relaxation via the cyclic AMP pathway in porcine coronary artery.
abstract: Puerarin, an isoflavonoid derived from the Chinese medicinal herb Radix puerariae, has been suggested to be useful in the management of various cardiovascular disorders. The present study examined the effect of acute exposure (30 min) to puerarin on vascular relaxation. Rings from porcine coronary artery of either sex were used. The highest concentration of puerarin (100 microM) produced a small but statistically significant relaxation of U46619-contracted rings. Vascular relaxations were also studied in the presence of lower concentrations of puerarin (0.1, 1 and 10 microM) which had no direct relaxation effect. Puerarin enhanced vasorelaxation to endothelium-independent relaxing agents, sodium nitroprusside and cromakalim. However, puerarin had no effect on vasorelaxation induced by endothelium-dependent relaxing agents, bradykinin and calcium ionophore A23187. The potentiating action of puerarin (10 microM) on sodium nitroprusside-mediated relaxation was not affected by the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 microM), or by the disruption of the endothelium with Triton X-100. The effect of puerarin was reversible following a washout period. The potentiating effects were comparable with the 3'-5'-cyclic adenosine monophosphate (cyclic AMP) analogues, 8-bromoadenosine-3'-5'-cyclic monophosphate (8-Br-cyclic AMP; 10 muM) and Sp-isomer [S nomenclature refers to phosphorus] of adenosine-3', 5'-cyclic monophosphorothioate (Sp-cyclic AMPS; 3 microM), but not the 3'-5'-cyclic guanosine monophosphate (cyclic GMP) analogue, 8-bromoguanosine-3'-5'-cyclic monophosphate (8-Br-cyclic GMP; 3 microM). The cyclic AMP antagonist, Rp-isomer [R nomenclature refers to phosphorus] of 8-bromoadenosine-3', 5'-cyclic monophosphorothioate (Rp-8-Br-cyclic AMPS; 10 microM), but not cyclic GMP antagonist, Rp-isomer of 8-bromoguanosine-3', 5'-cyclic monophosphorothioate (Rp-8-Br-cyclic GMPS; 10 microM), reversed the effects of puerarin (10 microM) on the enhancement of vasorelaxation to sodium nitroprusside. Our results demonstrated that puerarin enhanced sodium nitroprusside-induced relaxation, possibly via the cyclic AMP-dependent pathway.
authors.affiliation: Department of Pharmacology, 2/F Faculty of Medicine Building, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, People's Republic of China.
authors.forename: Dennis K Y
authors.initials: DK
authors.lastname: Yeung
authors.forename: Susan W S
authors.initials: SW
authors.lastname: Leung
authors.forename: Yan Chun
authors.initials: YC
authors.lastname: Xu
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
authors.forename: Ricky Y K
authors.initials: RY
authors.lastname: Man
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D029908:Pueraria / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D013873:Thionucleotides / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C105593:8-bromoadenosine-3',5'-cyclic monophosphorothioate; D004791:Enzyme Inhibitors; D007529:Isoflavones; D013873:Thionucleotides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester; C033607:puerarin