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

OBJECTIVES To investigate the potential for plant derived estrogens (phytoe strogens) genistein, phloretin, biochanin A and zearalanone to relax rabbit coronary arteries in vitro and to determine the mechanism(s) of such relax ation. BACKGROUND Epidemiological data suggests a reduction in the incidence of co ronary 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-ind ependent relaxation in rings with and without endothelium. Inhibition of ni tric oxide and prostaglandin synthesis with L-NAME and indomethacin had no effect on genistein-induced relaxation. Relaxation was unaffected by the sp ecific estrogen receptor antagonist ICI 182,780, the ATP-sensitive potassiu m channel inhibitor glibenclamide and the potassium channel inhibitor, bari um chloride. Calcium concentration-dependent contraction curves in high pot assium depolarization medium were significantly shifted to the right and do wnward after incubation with genistein and zearalanone. An inhibitory effec t of genistein (2 mu M) on L-type calcium current in guinea-pig ventricular myocytes confirmed a calcium antagonist relaxing mechanism of action. in h ealthy volunteers, plasma genistein levels of approximately 2 mu M are achi eved 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 car diovascular protective effect of these substances. (J Am Coll Cardiol 2000; 35:1977-85) (C) 2000 by the American College of Cardiology.