During maturation the vascular system undergoes structural and functional changes. Earlier we showed that endothelium of 1-2-week-old rats exerts an anticontractile effect due to tonic nitric oxide (NO) production which correlates with a higher eNOS expression level compared to adults. Estrogens are powerful regulators of eNOS expression and activity in arterial endothelium. This study tested the hypothesis that anticontractile effect of endothelium in young rats is associated with the influence of endogenous estrogens.

From the 2^nd postnatal day male Wistar rats were daily treated with estrogen receptor blocker ICI182,780 (1 mg/kg/day, s.c.), age-matched control pups were treated with vehicle. On 10–12 postnatal days saphenous artery was isolated for measuring the levels of eNOS and aromatase mRNA expression (qRT-PCR) and contractions to methoxamine (alpha₁-adrenoceptor agonist) before and after eNOS inhibition (wire myograph, DMT A/S, Denmark).

Serum estradiol concentration (ELISA) in young rats was 20% higher than in adults. mRNA expression levels of eNOS and aromatase, the key enzyme of estradiol synthesis, in pup arteries were much higher than in adults. Importantly, chronic ICI182,780 treatment reduced the impact of endothelium on methoxamine-induced contraction: eNOS inhibitor L-NNA had small effect in “ICI” group, but strongly potentiated the contraction in control. mRNA expression level of eNOS in ICI-treated group tended to be lower compared to control.

Our results suggest that estrogens (both blood-delivered and locally produced in the arterial wall) are important determinants of endothelial secretion in postnatal rats. Effects of estrogens lead to tonic NO production which weakens arteries responses to contractile influences.