Various studies have suggested that the phytoestrogen genistein has beneficial cardioprotective and vascular effects. However, there has been scarce information regarding the primary effect of genistein on coronary blood flow and its mechanisms including estrogen receptors, autonomic nervous system and nitric oxide (NO).

The present study was planned to determine the primary effect of genistein on coronary blood flow and the mechanisms involved. In anesthetized pigs, changes in left anterior descending coronary artery caused by intra-coronary infusion of genistein at constant heart rate and arterial pressure were assessed using ultrasound flowmeters. In 25 pigs, genistein infused at 0.075 mg/min increased coronary blood flow by about 16.3%. This response was graded in a further five pigs by increasing the infused dose of the genistein between 0.007 and 0.147 mg/min. In the 25 pigs blockade of cholinergic receptors (intravenous atropine; 5 pigs) and of -adrenergic receptors (intravenous phentolamine; 5 pigs) did not abolish the coronary response to genistein, whose effects were prevented by blockade of ₂-adrenergic receptors (intravenous butoxamine; 5 pigs), nitric oxide synthase (intracoronary L-NAME; 5 pigs) and estrogenic receptors (ER/ER; intracoronary fulvestrant; 5 pigs). In porcine aortic endothelial cells genistein induced the phosphorylation of eNOS and NO production through ERK 1/2, Akt and p38 MAPK pathways, which was prevented by the concomitant treatment by butoxamine and fulvestrant. In conclusion, genistein primarily caused coronary vasodilation the mechanism of which involved ER/ER and the release of NO through vasodilatory ₂-adrenoreceptor effects.