The effect of the phytoestrogen genistein on plasma nitric oxide concentrations, endothelin-1 levels and endothelium dependent vasodilation in postmenopausal women.
The phytoestrogen genistein improves endothelial dysfunction in ovariectomized rats through a nitric oxide-dependent mechanism. We investigated whether genistein alters the balance between the nitric oxide products and endothelin-1 and influences endothelium-dependent vasodilation in postmenopausal women. Sixty healthy postmenopausal women were enrolled in the study. A double-blind, placebo controlled, randomized design was employed. After a 4-week stabilization on a standard fat-reduced diet, participants to the study were randomly assigned to receive either genistein (n=30; 54 mg/day) or placebo (n=30). Flow-mediated, endothelium-dependent vasodilation of the brachial artery, plasma nitric oxide breakdown products and endothelin-1 levels were measured at baseline and after 6 months of genistein therapy. The mean baseline level of nitrites/nitrates was 22+/-10 micromol/l and increased to 41+/-10 micromol/ml after 6 months of treatment. The mean baseline plasma endothelin-1 level was 14+/-4 pg/ml and decreased to 7+/-1 pg/ml following 6 months of treatment with genistein. The mean baseline ratio of nitric oxide to endothelin also significantly increased at the end of treatment. Flow-mediated, endothelium-dependent vasodilation of the brachial artery was 3.9+/-0.8 mm at baseline and increased to 4.4+/-0.7 mm after 6 months of treatment. Placebo-treated women showed no changes in plasma nitrites/nitrates, endothelin-1 levels and flow-mediated vasodilation. Genistein therapy improves flow-mediated endothelium dependent vasodilation in healthy postmenopausal women. This improvement may be mediated by a direct effect of genistein on the vascular function and could be the result of an increased ratio of nitric oxide to endothelin.
Squadrito
Francesco
F
Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, School of Medicine, University of Messina, 98125 Gazzi, Italy. francesco.squadrito@unime.it
Altavilla
Domenica
D
Morabito
Nunziata
N
Crisafulli
Alessandra
A
D'Anna
Rosario
R
Corrado
Francesco
F
Ruggeri
Pietro
P
Campo
Giuseppe M
GM
Calapai
Gioacchino
G
Caputi
Achille P
AP
Squadrito
Giovanni
G
D001916:Brachial Artery / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D019833:Genistein / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007529:Isoflavones; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D048789:Phytoestrogens; D028321:Plant Preparations; D017698:Postmenopause / Q000097:blood / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*
D019332:Endothelin-1; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D009569:Nitric Oxide; D019833:Genistein