Acute responses to phytoestrogens in small arteries from men with coronary heart disease

The aim of this study was to investigate acute vasodilator responses to phytoestrogens and selective estrogen receptor-alpha (ER alpha) agonist in isolated small arteries from men with established coronary heart disease (CHD) and with a history of myocardial infarction versus healthy male control subjects. As to methodology, small arteries obtained from subcutaneous fat biopsies and mounted on a wire myograph were preconstricted with norepinephrine, and dilator responses to increasing nanomolar-micromolar concentrations of the phytoestrogens resveratrol and genistein (predominantly ER beta agonists) and to propyl-[1H]-pyrazole-1,3,5-triyl-trisplenol (PPT, a selective ER alpha agonist) were determined. These were compared with responses to reference compound 17 beta-estradiol (17 beta-E-2). Concentration-response curves were constructed before and after nitric oxide (NO) synthase inhibition with N-omega-nitro-L-arginine methyl ester. As a result, relaxation induced by the investigated compounds was similar in men with CHD and control men, but in both groups PPT and genistein-induced relaxation was greater than that of resveratrol and 17 beta-E-2. NO contributed to both phytoestrogens and PPT- induced relaxation but not to 17 beta-E-2 responses in arteries from control men. This NO-mediated component of relaxation was absent in arteries from men with established CHD. In conclusion, phytoestrogens, at concentrations achievable by ingestion of phytoestrogen-rich food products, evoke dilatation ex vivo of small peripheral arteries from normal men and those with established CHD. The contribution of NO to dilatory responses by these compounds is pertinent to arteries from control males, whereas other NO-independent dilatory mechanism(s) are involved in arteries from CHD.