© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Endothelium-dependent relaxation of rat aorta and main pulmonary artery by the phytoestrogens genistein and daidzein
aDepartment of Pharmacology, Guy's, King's and St. Thomas’ School of Biomedical Sciences, King's College London, St. Thomas's Hospital Campus, Lambeth Palace Road, London SE1 7EH, UK
* Corresponding author. Tel.: +44-207-960-5654 philip.aaronson{at}kcl.ac.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 µM L-NG-nitroarginine methyl ester (L-NAME) and/or 10 µM indomethacin on relaxation of PE (1 µM)-preconstricted contractures by genistein (1–100 µM) and daidzein (3–100 µM) were assessed by measuring isometric force development by rat arterial rings. The effect of L-NAME on relaxation to 17β-estradiol (10 µM) was also measured in aorta. Results and conclusions: Genistein and daidzein caused concentration-dependent relaxation of aorta rings preconstricted with PE (1 µM). The IC50 values were 5.7 µM (n=8, 95% confidence limits 4.3–7.7 µM) and 36.7 µM (n=12, 95% confidence limits 25.7–44.1 µM), respectively. Removal of the endothelium and pretreatment with L-NAME (100 µM) significantly inhibited relaxation at 3, 10 and 30 µM genistein and 10 and 30 µM 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. 17β-Estradiol (10 µM) 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 17β-estradiol, genistein, and daidzein were not significantly affected by the genomic estrogen receptor antagonist ICI 182,780 (10 µM). 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
KEYWORDS Contractile function; Endothelial function; Nitric oxide; Vasoconstriction/dilation
1 Present address: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar-243122 *UP), India.
2 Present address: Department Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK.
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