The endothelial cells help to control the tone of the underlying vascular smooth muscle by releasing vasoactive factors. In physiological circumstances, the release of relaxing factors (nitric oxide and endothelium-derived hyperpolarizing factor) appears to predominate. However, in certain blood vessels (peripheral veins and large cerebral arteries), the normal endothelium has the propensity to release vasoconstrictor substances, among which are superoxide anion and thromboxane A2; the release of these endothelium-derived vasoconstrictors may contribute to the autoregulatory processes. In most blood vessels, anoxic conditions initiate the release of an unidentified endothelium-dependent contracting factor. Cultured endothelial cells, and blood vessels maintained under culture conditions for prolonged periods of time, release the vasoconstrictor peptide endothelin. A characteristic of vascular diseases is that the ability of the endothelial cells to release relaxing factor(s) is reduced, while the generation of contracting factor is maintained or enhanced.