The endothelium can release potent vasodilator substances, in particular prostacyclin and endothelium-derived relaxing factor. The triggers for the release of endothelium-derived relaxing factor include increases in levels of shear stress, neurotransmitters, autacoids, platelet products, and hormones. The endothelium-dependent response to catecholamines involves stimulation of alpha 2-adrenoceptors on the endothelial cells. Indeed, in a number of blood vessels, selective alpha 2-adrenergic agonists cause endothelium-dependent relaxations. These are seen most typically in blood vessels with long-term exposure to high flows and high partial pressures of oxygen. In addition to the release of endothelium-derived relaxing factor, alpha 2-adrenergic agonists can stimulate postjunctional (postsynaptic) alpha 2-adrenoceptors on vascular smooth muscles. These receptors, which are more abundant in hypertensive blood vessels, activate the contractile process. However, the alpha 2-adrenergic vasoconstrictors act as partial agonists (with a limited receptor reserve) and hence their vasoconstrictor response is very sensitive to functional antagonists such as endothelium-derived relaxing factor. Thus, the presence of endothelial cells can blunt the vasoconstrictor response to these substances not only because of an augmented release of endothelium-derived relaxing factor but also because the vasoconstriction that they induce is particularly susceptible to the inhibitory effect of the factor.