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

J Am Coll Cardiol. 2000 Jun;35(7):1977-85. doi: 10.1016/s0735-1097(00)00645-8.


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 (30 mM), 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 microM) 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 microM 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Coronary Vessels / drug effects*
  • Coronary Vessels / physiology*
  • Estrogens, Non-Steroidal / pharmacology*
  • Female
  • Genistein / pharmacology
  • Humans
  • Isoflavones*
  • Male
  • Phytoestrogens
  • Plant Preparations
  • Plants*
  • Rabbits
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology*


  • Calcium Channel Blockers
  • Estrogens, Non-Steroidal
  • Isoflavones
  • Phytoestrogens
  • Plant Preparations
  • Vasodilator Agents
  • Genistein