Endothelium-dependent relaxation of rat aorta and main pulmonary artery bythe phytoestrogens genistein and daidzein

Citation
Sk. Mishra et al., Endothelium-dependent relaxation of rat aorta and main pulmonary artery bythe phytoestrogens genistein and daidzein, CARDIO RES, 46(3), 2000, pp. 539-546
Citations number
18
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CARDIOVASCULAR RESEARCH
ISSN journal
00086363 → ACNP
Volume
46
Issue
3
Year of publication
2000
Pages
539 - 546
Database
ISI
SICI code
0008-6363(200006)46:3<539:ERORAA>2.0.ZU;2-S
Abstract
Objective: The dietary phytoestrogens genistein and daidzein have been show n to relax agonist-preconstricted arteries in vitro; the mechanisms of rela xation remain incompletely understood. This study aimed to determine whethe r the relaxation of phenylephrine (PE)-constricted rat aorta and main pulmo nary artery by genistein and daidzein was endothelium-dependent. Methods: E ffects of endothelial-denudation, and pretreatment with with 100 mu M L-N-G -nitroarginine methyl ester (L-NAME) and/or 10 mu M indomethacin on relaxat ion of PE (1 mu M)-preconstricted contractures by genistein (1-100 mu M) an d daidzein (3-100 mu M) were assessed by measuring isometric force developm ent by rat arterial rings. The effect of L-NAME on relaxation to 17 beta-es tradiol (10 mu M) was also measured in aorta. Results and conclusions: Geni stein and daidzein caused concentration-dependent relaxation of aorta rings preconstricted with PE (1 mu M) The IC50 values were 5.7 mu M (n = 8, 95% confidence limits 4.3-7.7 mu M) and 36.7 mu M (n = 12, 95% confidence limit s 25.7-44.1 mu M), respectively. Removal of the endothelium and pretreatmen t with L-NAME (100 mu M) significantly inhibited relaxation at 3, 10 and 30 mu M genistein and 10 and 30 mu M daidzein. The contracture evoked in rat aorta by depolarization with 75 mM K+ solution was similarly relaxed by gen istein in a partially endothelium-dependent manner. 17 beta-Estradiol (10 m u M) 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 bro ught about by 17 beta-estradiol, genistein, and daidzein were not significa ntly affected by the genomic estrogen receptor antagonist ICI 182,780 (10 m u M). Similar endothelium-dependent effects of genistein were observed in t he main pulmonary artery. The results show that the relaxation of these rat arteries by concentrations of genistein and daidzein which overlap those p resent in human plasma after ingestion of soybean-containing meals is large ly endothelium dependent (C) 2000 Elsevier Science B.V. All rights reserved .