The phytoestrogen genistein enhances endothelium-independent relaxation in the porcine coronary artery.
Genistein, a phytoestrogen, possesses cardioprotective effects. Responses to genistein (0.1-100 microM) were assessed in 9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy prostaglandin F(2 alpha) (U46619)-contracted porcine coronary arterial rings, with significant relaxations at high concentrations. At concentrations with little relaxation, genistein (0.3-3 microM) did not affect relaxation produced by bradykinin and the calcium ionophore, A23187. In contrast, sodium nitroprusside- and cromakalim-induced relaxations were enhanced by genistein (3 microM). N(omega)-nitro-L-arginine methyl ester (L-NAME) (300 microM) or Triton X-100 (0.5%) did not affect the enhancement of relaxation by genistein. The tyrosine kinase inhibitor, tyrphostin 23 (30 microM), had no effect on sodium nitroprusside-elicited relaxation. In summary, genistein relaxed porcine coronary artery at relatively high concentrations. At a physiologically relevant concentration (3 microM), it is devoid of significant vascular effect, but enhanced endothelium-independent relaxations. This effect of genistein does not involve the nitric oxide synthase (NOS) pathway and the endothelium, and is mediated through a mechanism different from tyrosine kinase inhibition.
Lee
Mary Y K
MY
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 2/F Laboratory Block, Faculty of Medicine Complex, 21 Sassoon Road, Hong Kong SAR, China.
Man
Ricky Y K
RY
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D048789:Phytoestrogens; D028321:Plant Preparations / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D009599:Nitroprusside; D019833:Genistein