ABSTRACT
Estrogens have protective effects on the cardiovascular system in part by improving the endothelial function. Chronic estrogen treatment potentiates endothelium-dependent relaxation by stimulating the endothelial formation of nitric oxide (NO) and prostacyclin. The present study examines whether administration of 17-estradiol affects also endotheliumderived hyperpolarizing factor (EDHF)-induced suppression of vascular tone. Rings of mesenteric artery from either sham-operated rats, dosed with solvent (sesame oil), control ovariectomized rats, dosed with sesame oil, and ovariectomized rats, dosed with 17-estradiol, were suspended in organ chambers for the measurement of changes in isometric tension in the presence of indomethacin. In the sham-operated group (one and four weeks treatments), Nnitro-L-arginine (an inhibitor of nitric oxide synthase) and the combination of charybdotoxin (an inhibitor of large and intermediate conductance calcium-activated potassium channels) plus apamin (an inhibitor of small conductance calcium-activated potassium channels) significantly shifted to the left the concentration-contraction curve to phenylephrine. N-nitro-Larginine also increased contractile responses to phenylephrine in the control group of ovariectomized rats after 1 week of treatment whereas no such effect was obtained after 4 weeks of treatment. Charybdotoxin and apamin affected contractile responses to phenylephrine neither after 1 week nor 4 weeks of treatment in the control group of ovariectomized rats. Estrogen-substitution restored the potentiation by N-nitro-L-arginine of contractile responses to phenylephrine and that by the combination of charybdotoxin and apamin after 4 weeks of treatment. These experiments suggest that restoration of physiological estrogen levels by estrogen-replacement therapy is able to prevent the loss of the basal influence of both NO and EDHF in the mesenteric artery of ovariectomized rats.
