Mediators produced by the endothelial cell.

Abstract

SUMMARY This review discusses the role of three mediators, synthesized by vascular endotheiial cells, that help to keep the surface of the normal endotheliuin nonthrombogenic. The first is prostacydin, a product of arachldonic add metabolism discovered hi 1976. This labile prostanoid, with a half-life of approximately 3 minutes, relaxes vascular smooth musde and inhibits the aggregation of blood platelets. Prostacydin and its analogues are currently being tested clinically for use hi cardiovascular diseases such as primary pulmonary hypertension. The second mediator discussed is endothelium-derived relaxing factor (EDRF), discovered in 1980, which also relaxes smooth muscle and inhibits the aggregation and adhesion of platelets. Substances that stimulate the release of EDRF include acetykhoUne, bradykinin, and adenosine 5'-diphosphate. EDRF is even more labile than prostacydin, with a half-life of about 6 seconds, and it has recently been identified as nitric oxide. Prostacydin and EDRF are released together following stimulation of endothelial receptors and synergize to inhibit platelet aggregation. 13-Hydroxy-9,11-octadecadienoic add, a third suggested mediator, is not released but acts from inside the cell to make the endothelial surface nonadhesive for circulating blood ceils. It is proposed that these three mediators form the endothelial defense mechanism against blood-borne cells and chemicals and that breakdown of this barrier results in diseases such as hypertension and atherosclerosis. (Hypertension 12: 530-548,1988) KEY WORDS • prostacyclin • endothelium-derived relaxing factor • thromboresistance • 13-hydroxy-9,ll-octadecadienoic add • endothelin • 6-keto-prostaglandin E,

Specific receptors for endothelin‐3 in cultured bovine endothelial cells and its cellular mechanism of action

“…Our data are consistent with the contention that mobilization of intracellular Ca 2+ is required for the production and/or release of endothelium-derived vasodilators, such as EDRF and prostacyclin [12]. Thus, the presence of specific ET-3 receptors in EC strongly suggests that ET-3 plays an important role in the regulation of vasodilatation, possibly via receptormediated release of EDRF and/or prostacyclin from EC.…”

Evaluation of Oxidative Stress in Type 2 Diabetes Mellitus and Follow-up Along with Vitamin E Supplementation

“…The two of the most antiaggregants are the eicosanoids, prostacyclins (PGI 2 ) and nitric oxide. In healthy vessels, PGI 2 and nitric oxide combine to prevent platelet adherence to endothelium and platelet aggregation [20]. Platelet from diabetic subjects have been reported to have diminished sensitivity to PGI 2 and NO [21] hence platelet aggregation is increased in type 2 DM.…”

Different patterns of release of endothelium‐derived relaxing factor and prostacyclin

“…Prostacyclin (PGI2; Moncada et al, 1976) and endotheliumderived relaxing factor (EDRF; Furchgott & Zawadzki, 1980) are both released from endothelial cells (EC) by a variety of agonists including acetylcholine (ACh), adenosine diphosphate (ADP), bradykinin (BK) and substance P (see Furchgott et al, 1984;Gryglewski et al, 1988). This receptor-mediated release of EDRF and PGI2 is coupled most probably at the level of phospholipase C (de Nucci et al, 1988a).…”