Besides causing relaxation of the underlying smooth muscle through the release of endothelium-derived relaxing factors (EDRFs), the endothelial cells of certain blood vessels, under given circumstances, can also trigger the contraction (constriction) of these muscle cells. Such acute, endothelium-dependent, increases in contractile tone can be due to the suppression of nitric oxide production (constitutive or stimulated), or to the production of vasoconstrictor peptides (angiotensin II or endothelin-1) or oxygen-derived free radicals (superoxide anions) and/or vasoconstrictor products of arachidonic acid metabolism (endoperoxides, thromboxane A2, and possibly isoprostanes). The latter have been termed endothelium-derived contracting factors (EDCFs) as they can contribute to moment-to-moment changes in contractile activity of the vascular smooth muscle cells that surround the endothelium from which they originate. EDCF-mediated responses are most pronounced in large cerebral arteries, and are enhanced by aging, spontaneous hypertension, and diabetes. They contribute to the blunting of endotheliumdependent vasodilations in aged subjects and subjects with essential hypertension. Since EDCFs cause contraction of vascular smooth muscle by activation of thromboxane-prostanoid (TP) receptors, selective antagonists at these receptors are able to prevent endothelium- dependent contractions, thus opening up prospects for potential therapeutic implications...