Question: 

The circulatory system undergoes considerable changes during postnatal maturation. Structural changes are represented by a thickening of the vascular walls. In addition, a more than 2-fold increase in blood pressure is observed during maturation. Recently, it was shown that some signalling pathways governing vessel contraction experience developmental changes. However, the mechanisms responsible for the developmental change of blood pressure are still incompletely understood. Thus, we tested the hypothesis that activation of the endothelium in young animals is one of the mechanisms attenuating arterial contractility and, thereby, keeping blood pressure low.

Methodology: 

We studied methoxamine-induced contractions of isometric preparations of rat saphenous arteries in adult (2-3-month-old) and young (1-2-week-old) animals.

Results: 

In young rats, MX-induced contractions were smaller in endothelium-intact compared to endothelium denuded vessels. In contrast, the endothelium had no effect on MX-induced contractions in adult rats. The reduced MX-induced contractions of endothelium-intact vessel from young rats persisted in the presence of indomethacin, a cyclooxygenase inhibitor, of TRAM-34, an inhibitor of SK channels, of UCL-1684, an inhibitor of IK channels and of 18a-glycyrrhetinic acid, an inhibitor of gap-junctions. In contrast, the NO-synthase inhibitor L-NNA prominently increased MX-induced contractions in endothelium-intact arteries of young rats; the inactive L-NNA analogue D-NNA was without effect. A similar increase of MX-induced contractions was observed in the presence of ODQ, an inhibitor of guanylate cyclase. Moreover, the effect of the endothelium on MX-induced contractions of vessel from young rats was reduced by LY-294002, an inhibitor of PI3-kinase, but not by ruthenium red, an inhibitor of TRPV4 channels. In addition, L-NNA caused an increase of basal tone in endothelium-intact vessels of young rats; D-NNA was without effect on basal tone.

Conclusion: 

We propose that arteries of young rats experience a spontaneous and persistent release of NO not present in vessels of adult rats. This mechanism leads to an attenuation of arterial contractility in young animals. The disappearance of this endothelial brake on vasoconstrictor-induced contractions may contribute to the blood pressure increase during maturation.