Genistein reduces agonist-induced contractions of porcine coronary arterial smooth muscle in a cyclic AMP-dependent manner.
Low concentrations of genistein enhance the vasodilatation induced by endothelium-independent vasodilators. The present study examined whether or not low concentrations of genistein modulate contractions in isolated porcine coronary arteries. The role of second messengers in the response to genistein was also assessed. Arterial rings were studied in organ baths and contracted with KCl, U-46619 (9,11-dideoxy-9alpha, 11alpha-methanoepoxy prostaglandin F2alpha), 5-hydroxytryptamine (5-HT) or endothelin-1 in the absence or presence of genistein (< or =3 microM). Genistein significantly reduced agonist-induced but not KCl-induced contraction. Inhibition of endothelial nitric oxide synthase and disruption of endothelial function by Triton-X100 did not affect the modulation of contraction by genistein. The genistein-induced attenuation of contraction could be mimicked by both cAMP and cGMP analogs. However, only the cAMP-dependent protein kinase inhibitor, Rp-8-Br-cAMPS, abolished the effect of genistein. These results suggest that genistein reduces agonist-induced contraction by an endothelium-independent manner. This action is mediated via the cAMP-dependent signal transduction pathway.
Lee
Mary Y K
MY
Department of Pharmacology, 2/F Laboratory Block, Faculty of Medicine Building, The University of Hong Kong, 21 Sassoon Road, Hongkong SAR, China.
Leung
Susan W S
SW
Vanhoutte
Paul M
PM
Man
Ricky Y K
RY
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D017830:Octoxynol; D011189:Potassium Chloride / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D020032:Tyrphostins / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D020032:Tyrphostins; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D012701:Serotonin; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D017830:Octoxynol; D019833:Genistein; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D011505:Protein-Tyrosine Kinases; D006152:Cyclic GMP; C060641:tyrphostin A23; D019331:NG-Nitroarginine Methyl Ester