Endothelial cells release

Furchgott and Zawadzki [1] first discovered that endothelial cells release a substance(s) responsible for the relaxation of vascular smooth muscle by acetylcholine this substance was named endothelium-derived relaxing factor (EDRF). This epoch-making discovery answers the question raised for nearly one hundred years by pharmacologists about why vascular smooth muscle is relaxed by acetylcholine, which however elicits contraction of the other smooth muscles. Because of its instability, the true chemical nature of EDRF was not easily identified. Several years later, several research groups independently found that the biological activities and biochemical properties of EDRF were identical... 

Figure 22.4 Injury to endothelial cells can lead to vasospasm. Normal endothelial cells release nitric oxide (NO) which relaxes smooth muscle this is achieved by nitric oxide increasing the concentration of cyclic GMP within smooth muscle fibres and cyclic GMP relaxing the smooth muscle. Injured endothelial cells secrete very little nitric oxide but secrete more endothelin. The latter increases the formation of inositol trisphosphate (IP3), which binds to the sarcoplasmic reticulum (SR) where it stimulates the Ca ion channel. The Ca ion channel in the plasma membrane is also activated. Both effects result in an increase in cytosolic Ca ion concentration, which then stimulates contraction (vasospasm). This reduces the diameter of the lumen of the artery.

The mechanism by which organic nitrates relieve the pain of angina pectoris was not discovered until nitric oxide was identified as the agent which was responsible for vasodilation of arteries. It was known for many years that endothelial cells released a factor that resulted in vasodilation a factor appropriately called endothelial relaxing factor (EDRF). It was, however, some time before the factor was identified, probably because it turned out to be a gas - nitric oxide - which was totally unexpected. Nitric oxide is now known to be a very important messenger molecule involved in the regulation of many other systems. The mechanism by which it causes vasodilation is described in Chapter 13. 

Jimenez JJ, Jy W, Mauro LM, Soderland C, Horstman LL, Ahn YS. Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. Thromb Res 2003 109 175-180. 

P-selectin plays an essential role in the initial recruitment of leukocytes. When endothelial cells are activated by molecules such as histamine or thrombin during inflammation, P-selectin moves from an internal cell location to the endothelial cell surface. Thrombin is one trigger of endothelial-cell release of P-selectin. Ligands for P-selectin on eosinophils and neutrophils are similar they are sialylated carbohydrates, but clearly different from those reported for E-selectin. P-selectin attaches to the actin cytoskeleton through anchor proteins. 

Von Willebrand factor is the adhesive protein with an essential role in promoting interactions between platelets and vascular subendothelium. VWF is synthesized by endothelial cells and megakaryocytes. Endothelial cells release their synthesized VWF to the plasma and the vessel subendothelium, while the VWF produced by megakaryoc34es is stored in the platelet alpha granules [20]. VWF is thus physiologically distributed in plasma, subendothelium and platelets. Adequate hemostasis requires balanced interactions among the VWF located in these three compartments. 

Endothelial cells release the synthesized VWF towards the luminal portion as well as towards the abluminal (subendothelial) portion. Several studies suggest drat subendothelial VWF can support platelet adhesion regardless of plasma VWF. 

Figure 3.1. Schematic representation of the cellular components of the blood-hrain (Panel A) and blood-cerehral spinal fluid (Panel B) barriers. The blood-brain barrier consists of continuous type endothelial cells with complex tight junctions to limit paracellular diffusion. The astrocytes and pericytes located in close proximity to the brain endothelial cells release various endogenous factors that modulate endothelial cell permeability. In contrast, the choroid endothelial cells are fenestrated and the blood-cerebral spinal fluid barrier properties are provided by the tight junctions formed between the choroid epithelial cells.

Desmopressin stimulates the endothelial cell release of von WiUebrand factor and factor VIIt. ° It is effective for patients with von WiUebrand disease who have adeqnate endogenous stores of functional von Willebrand factor. This group includes most patients with type 1 disease and some patients with type 2A disease. Conversely, desmopressin is not appropriate for patients with type 3 disease, who lack stores of von WiUebrand factor. 

Ziegelstein RC, Corda S, Pili R, Passaniti A, Lefer D, Zweier JL, Fraticelli A, Capogrossi MC Initial contact and subsequent adhesion of human neutrophils or monocytes to human aortic endothelial cells releases an endothelial intracellular calcium store. Circulation 1994 90 1899-1907. 

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