Objective: The endothelium produces vasoactive factors and thereby modulates vessels contractility. In larger vessels like the saphenous artery, NO is the main factor released upon endothelial stimulation. In smaller arteries, gap junctions between endothelial and smooth muscle cells (SMC) coordinate SMC and endothelial function during vessel relaxation and contraction. Recently it was shown that some mechanisms underlying vessel contraction undergo developmental changes. In this study we tested the hypothesis that the mechanisms coordinating SMC and endothelial function also change with arterial growth during postnatal development. Methods: We studied methoxamine-induced contractions of rat saphenous arteries in adult (2-month-old) and young (2-week-old) animals. Methoxamine (MX) is a selective a₁-adrenoceptor agonist expressed in SMC but not in the endothelium. Results: We discovered that the endothelium does not contribute to the MX-induced contraction in adult rats. However, the sensitivity to MX in young rats was smaller in endothelium-intact compared to endothelium denuded vessels (DpD₂ = 0.70±0.37, n=8). In young rats, the smaller MX sensitivity in endothelium-intact vessels persisted after blockade of SK_Ca (small conductance calcium-activated potassium channels) with TRAM-34 or IK_Ca (intermediate conductance calcium-activated potassium channels) with UCL-1684. In contrast, the NO-synthase inhibitor L-NNA prominently increased MX-sensitivity in endothelium-intact arteries of young rats (DpD₂ = 0.43±0.13, n=6); the inactive L-NNA analogue D-NNA was without effect. Conclusion: We conclude that the contribution of the endothelium to MX-induced saphenous artery contraction changes during development resulting in an increased MX-sensitivity of the artery with age. The inhibitory effect of the endothelium on MX-induced contractions in younger rats is due to NO-release but not to an activity of SK_Ca or IK_Ca.