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Endothelium-dependent relaxation of rat aorta and main pulmonary artery by the phytoestrogens genistein and daidzein. 2000

S K Mishra, and S E Abbot, and Z Choudhury, and M Cheng, and N Khatab, and N J Maycock, and A Zavery, and P I Aaronson
Department of Pharmacology, Guy's, King's and St. Thomas' School of Biomedical Sciences, King's College London, UK.

OBJECTIVE The dietary phytoestrogens genistein and daidzein have been shown to relax agonist-preconstricted arteries in vitro; the mechanisms of relaxation remain incompletely understood. This study aimed to determine whether the relaxation of phenylephrine (PE)-constricted rat aorta and main pulmonary artery by genistein and daidzein was endothelium-dependent. METHODS Effects of endothelial-denudation, and pretreatment with with 100 microM L-N(G)-nitroarginine methyl ester (L-NAME) and/or 10 microM indomethacin on relaxation of PE (1 microM)-preconstricted contractures by genistein (1-100 microM) and daidzein (3-100 microM) were assessed by measuring isometric force development by rat arterial rings. The effect of L-NAME on relaxation to 17beta-estradiol (10 microM) was also measured in aorta. CONCLUSIONS Genistein and daidzein caused concentration-dependent relaxation of aorta rings preconstricted with PE (1 microM). The IC50 values were 5.7 microM (n=8, 95% confidence limits 4.3-7.7 microM) and 36.7 microM (n=12, 95% confidence limits 25.7-44.1 microM), respectively. Removal of the endothelium and pretreatment with L-NAME (100 microM) significantly inhibited relaxation at 3, 10 and 30 microM genistein and 10 and 30 microM daidzein. The contracture evoked in rat aorta by depolarization with 75 mM K+ solution was similarly relaxed by genistein in a partially endothelium-dependent manner. 17Beta-estradiol (10 microM) caused a 48.7+/-5.0% (n=11) relaxation of the PE contracture, which was significantly reduced to 25.1+/-5.3% (n=7) by L-NAME. Relaxations brought about by 17beta-estradiol, genistein, and daidzein were not significantly affected by the genomic estrogen receptor antagonist ICI 182,780 (10 microM). Similar endothelium-dependent effects of genistein were observed in the main pulmonary artery. The results show that the relaxation of these rat arteries by concentrations of genistein and daidzein which overlap those present in human plasma after ingestion of soybean-containing meals is largely endothelium dependent.

UI MeSH Term Description Entries
D007213 Indomethacin A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D007529 Isoflavones 3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. 3-Benzylchroman-4-One,3-Benzylidene-4-Chromanone,Homoisoflavone,Homoisoflavones,Isoflavone,Isoflavone Derivative,3-Benzylchroman-4-Ones,3-Benzylidene-4-Chromanones,Isoflavone Derivatives,3 Benzylchroman 4 One,3 Benzylchroman 4 Ones,3 Benzylidene 4 Chromanone,3 Benzylidene 4 Chromanones,Derivative, Isoflavone,Derivatives, Isoflavone
D008297 Male Males
D011651 Pulmonary Artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Arteries, Pulmonary,Artery, Pulmonary,Pulmonary Arteries
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D004958 Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. 17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001011 Aorta The main trunk of the systemic arteries. Aortas
D014662 Vasoconstrictor Agents Drugs used to cause constriction of the blood vessels. Vasoactive Agonist,Vasoactive Agonists,Vasoconstrictor,Vasoconstrictor Agent,Vasoconstrictor Drug,Vasopressor Agent,Vasopressor Agents,Vasoconstrictor Drugs,Vasoconstrictors,Agent, Vasoconstrictor,Agent, Vasopressor,Agents, Vasoconstrictor,Agents, Vasopressor,Agonist, Vasoactive,Agonists, Vasoactive,Drug, Vasoconstrictor,Drugs, Vasoconstrictor
D014664 Vasodilation The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE. Vasodilatation,Vasorelaxation,Vascular Endothelium-Dependent Relaxation,Endothelium-Dependent Relaxation, Vascular,Relaxation, Vascular Endothelium-Dependent,Vascular Endothelium Dependent Relaxation

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