Endothelium-dependent contractions: From superoxide anions to TP-receptor agonists

Abstract

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 endothelium-dependent 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.