17β-Estradiol increases nitric oxide and prostaglandin I2 production by cultured human uterine arteries only in histologically normal specimens

These experiments were designed to investigate whether 17 beta -estradiol (E-2) modulates the endothelial function of perimenopausal human uterine arteries. After the artery specimen was cultured in the presence or absence of E-2 at a physiologic concentration of 200 pg/ml, changes in isometric tension and cyclic nucleotide production were determined. Degree of intimal hyperplasia was assessed histologically and expressed as intima-to-media ratio. Acetylcholine produced an endothelium-dependent relaxation in six specimens (group I) of 12, which was inhibited by N-G-nitro-L-arginine or indomethacin. However. the agonist failed to produce a definite relaxation in the remaining 6 (group II) The endothelium-dependent relaxation was significantly augmented after incubating with E-2 only in group I specimens. Cyclic nucleotide production was significantly increased after E-2 incubation only in group I specimens, whereas it was inhibited by N-G-niho-L-arginine or indomethacin. Histologic study revealed that the six specimens of group I had normal intima (intima-to-media ratio = 19.1 +/-1.8%) and the remaining six of group II had intimal hyperplasia (intima-to-media ratio = 53.6 +/-5.3%). Increased production of cyclic nucleotides occurred in uterine arteries with normal intima but not in arteries with intimal hyperplasia derived from perimenopausal women.