Acute, nongenomic vasodilatory action of estradiol is attenuated by chronic estradiol treatment

Deficiency of estradiol or chronic estrogen treatment may alter the respons es to this hormone in many tissues. A possible interaction between the acut e nongenomic and the chronic effects of estradiol on microvessels have not been investigated yet. In the present study we have investigated whether ac ute in vitro vasodilatory action of estradiol on a small artery is altered by chronic estradiol pretreatment, Female rats were surgically ovariectomiz ed and subjected to either estradiol replacement therapy (estradiol propion ate, 450 mug/kg/week) or vehicle administration for 5 weeks, Cylindrical se gments of the saphenous artery were studied using videocomputerized microar teriography in vitro, Estradiol, in concentrations of 10(-6) to 10(-4) M re laxed norepinephrine precontracted vessel segments in a dose-dependent mann er. Magnitude of relaxation observed in arteries of estradiol replaced anim als was significantly smaller at all concentrations than that of nonreplace d ovariectomized rats; maximal relaxation in the control ovariectomized gro up was 64.5% +/- 3.6%, while it was 34.3% +/- 4.2% only in the ovariectomiz ed and estradiol replaced group (P < 0.001), Comparison of acute relaxation s in response to papaverine and nifedipine failed to prove a reduced activi ty of the general relaxation machinery in estradiol replaced animals. We co nclude that chronic estradiol replacement can downregulate the acute nongen omic vasorelaxation effect of this hormone in small arteries of ovariectomi zed rats.