ESTRADIOL INHIBITS SMOOTH-MUSCLE CELL-PROLIFERATION OF PIG CORONARY-ARTERY

1 The effect of oestradiol 17beta on vascular smooth muscle proliferat ion was examined in segments of the pig left anterior descending coron ary artery (LAD). It was established by cytochemical techniques that o ut-growth from the segments was composed of vascular smooth muscle cel ls. 2 [H-3]-thymidine uptake by pig LAD segments was used as an index of vascular smooth muscle cell proliferation. Nitroprusside and forsko lin significantly inhibited [H-3]-thymidine uptake and were used as po sitive controls. 3 Oestradiol 17beta (180-360 nM) inhibited thymidine uptake by pig LAD segments (P<0.05). The inhibition was observed only in the absence of phenol red, which is a weak oestrogen receptor agoni st. The anti-oestrogens tamoxifen and its more potent metabolite 4-hyd roxytamoxifen, both of which are partial oestrogen receptor agonists, also significantly inhibited thymidine uptake. However, pretreatment w ith either tamoxifen or 4-hydroxytamoxifen did not signficantly block oestradiol 17beta-induced inhibition of thymidine uptake. 4 The LAD se gments bound [H-3]-oestradiol 17beta in a time-dependent manner and ab out 20 to 30% was displaced by an excess of unlabelled oestradiol 17be ta. Autoradiography showed [H-3]-oestradiol 17beta was evenly distribu ted in the cytosol and nuclei of cells in the three layers of the vess el wall. 5 The data suggest that oestradiol 17beta inhibits smooth mus cle cell proliferation in porcine LAD segments, possibly through an oe strogen receptor mechanism. This in vitro effect suggests an in vivo r ole for oestradiol 17beta in directly protecting coronary arteries aga inst myointimal proliferation in premenopausal women.