VASODILATOR AND ANTIOXIDANT EFFECTS OF THE ISOFLAVONE METABOLITE EQUOL IN HYPERTENSIVE RATS

Abstract

Daidzein is found in high levels in soy. It is extensively metabolised in the gut, yielding a number of relatively unstudied active metabolites. The metabolite equol is thought to be an important contributor to the protective effects of dietary soy in the cardiovascular system. We tested the acute effects of daidzein and equol on carotid and cerebral vascular tone and superoxide production in normotensive and hypertensive rats. Both compounds (0.1–300 μM) were equipotent dilators of carotid artery isolated from normotensive rats. However the vasodilator efficacy of equol was preserved, whereas responses to daidzein were impaired, in hypertensive rats. Using a cranial window preparation we also studied effects on basilar artery diameter in vivo. Equol and daidzein (10–100 μM) dilated the basilar artery with similar potency in both normotensive and hypertensive rats. We postulated that equol might be a more potent dilator than daidzein in hypertensive carotid arteries due to a greater ability to scavenge reactive oxygen species in the artery wall. This was tested using lucigenin-enhanced chemiluminescence. NADPH-induced superoxide production was higher in hypertensive versus normotensive rats and in basilar versus carotid arteries. However, neither equol nor daidzein reduced superoxide production in carotid artery from normotensive or hypertensive rats. Interestingly, equol attenuated superoxide production in basilar arteries from hypertensive rats, whilst having no effect in vessels from normotensive rats. Inhibition of superoxide production and preserved vasodilator capacity by equol in hypertensive arteries is compatible with its potential as a therapeutic agent in cerebrovascular disease.