A study of the mechanism of estrogen as an antiatherosclerotic: the inhibitory effect of estrogen on A23187-induced contraction of the aortic wall.

Although the antiatherosclerotic effects of estrogen are well known, the mechanisms involved have not been determined. We designed experiments in which strips of thoracic aorta from oophorectomized rabbits were contracted by the calcium ionophore A23187 and the inhibition of the contraction by estrogen and concomitant levels of cyclic nucleotides were determined. A23187 (10(-5) M) increased the tension slowly but progressively, and there was a concomitant decrease in cyclic AMP levels. While a dose-dependent relaxation occurred in strips contracted by A23187 with addition of theophylline (greater than 10(-4) M) or dibutyryl cyclic AMP (greater than 10(-4) M) to the bath, prior addition of these compounds inhibited the contraction. Pretreatment of the strips with estrogen (2 x 1-(-7) M, 2 x 10(-5) M) significantly prevented contraction of the strips, as induced by A23187, and also prevented reduction in cyclic AMP levels, as induced by the ionophore. Cyclic GMP levels remained unchanged throughout. As the contraction of these tissues wall was inhibited by estrogen in an apparent association with a reduction in the levels of cyclic AMP, this might help to explain the antiatherosclerotic effects of estrogen, as reduction in these nucleotide levels has been suggested to induce atherosclerotic lesions in the arterial wall by enhancing vascular permeability.