Deficiency of estradiol or chronic estrogen treatment may alter the responses to this hormone in many tissues. A possible interaction between the acute nongenomic and the chronic effects of estradiol on microvessels have not been investigated yet. In the present study we have investigated whether acute in vitro vasodilatory action of estradiol on a small artery is altered by chronic estradiol pretreatment. Female rats were surgically ovariectomized and subjected to either estradiol replacement therapy (estradiol propionate, 450 micrograms/kg/week) or vehicle administration for 5 weeks. Cylindrical segments of the saphenous artery were studied using videocomputerized microarteriography in vitro. Estradiol, in concentrations of 10(-6) to 10(-4) M relaxed norepinephrine precontracted vessel segments in a dose-dependent manner. Magnitude of relaxation observed in arteries of estradiol replaced animals was significantly smaller at all concentrations than that of nonreplaced ovariectomized rats; maximal relaxation in the control ovariectomized group was 64.5% +/- 3.6%, while it was 34.3% +/- 4.2% only in the ovariectomized and estradiol replaced group (P < 0.001). Comparison of acute relaxations in response to papaverine and nifedipine failed to prove a reduced activity of the general relaxation machinery in estradiol replaced animals. We conclude that chronic estradiol replacement can downregulate the acute nongenomic vasorelaxation effect of this hormone in small arteries of ovariectomized rats.