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

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 mu M L-N-G-nitroarginine methyl ester (L-NAME) and/or 10 mu M indomethacin on relaxation of PE (1 mu M)-preconstricted contractures by genistein (1-100 mu M) and daidzein (3-100 mu M) were assessed by measuring isometric force development by rat arterial rings. The effect of L-NAME on relaxation to 17 beta-estradiol (10 mu M) was also measured in aorta. Results and conclusions: Genistein 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 limits 25.7-44.1 mu M), respectively. Removal of the endothelium and pretreatment 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 genistein in a partially endothelium-dependent manner. 17 beta-Estradiol (10 mu 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 brought about by 17 beta-estradiol, genistein, and daidzein were not significantly affected by the genomic estrogen receptor antagonist ICI 182,780 (10 mu M). 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 (C) 2000 Elsevier Science B.V. All rights reserved.