Plant-derived estrogens relax coronary arteries in vitro by a calcium antagonistic mechanism

OBJECTIVES To investigate the potential for plant derived estrogens (phytoestrogens) genistein, phloretin, biochanin A and zearalanone to relax rabbit coronary arteries in vitro and to determine the mechanism(s) of such relaxation. BACKGROUND Epidemiological data suggests a reduction in the incidence of coronary heart disease in humans who have a high intake of phytoestrogens. METHODS Isolated rabbit coronary artery rings were suspended in individual organ baths, precontracted with potassium chloride (30mM), and the relaxing effects and mechanisms of relaxation to genistein, phloretin, biochanin A and zearalanone were determined by measurement of isometric tension. RESULTS Genistein, phloretin and biochanin A induced significant gender-independent relaxation in rings with and without endothelium. Inhibition of nitric oxide and prostaglandin synthesis with L-NAME and indomethacin had no effect on genistein-induced relaxation. Relaxation was unaffected by the specific estrogen receptor antagonist ICI 182,780, the ATP-sensitive potassium channel inhibitor glibenclamide and the potassium channel inhibitor, barium chloride. Calcium concentration-dependent contraction curves in high potassium depolarization medium were significantly shifted to the right and downward after incubation with genistein and zearalanone. An inhibitory effect of genistein (2 mu M) on L-type calcium current in guinea-pig ventricular myocytes confirmed a calcium antagonist relaxing mechanism of action. in healthy volunteers, plasma genistein levels of approximately 2 mu M are achieved after ingestion of a commercially available soy protein drink (Supro) containing 37 mg genistein. CONCLUSIONS This study demonstrates that phytoestrogens induce endothelium-independent relaxation of coronary arteries; the mechanism involves calcium antagonism. These mechanisms may contribute to the potential long-term cardiovascular protective effect of these substances. (J Am Coll Cardiol 2000;35:1977-85) (C) 2000 by the American College of Cardiology.