Vascular endothelium

The term NOS is used to denote a family of three related but distinct isoenzymes neuronal NOS (nNOS) endothelial NOS (eNOS, endothelium and platelets) and inducible NOS (iNOS, endothelium, vascular smooth muscle and macrophage). In addition to reduced nicotinamide adenine dinucleotide phosphate (NADPH) shown in Figure 5.5, NOS enzymes also require flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and tetrahydrobiopterin (BH4) as coenzymes. 

ECE inhibitors can be evaluated in enzyme assays, isolated tissues and whole animals. A range of tissues (for example, vascular endothelium, vascular smooth muscle, lung) demonstrate phosphoramidon-sensitive ECE activity and provide a choice of starting points for an enzyme assay for ECE inhibitors. Partially purified ECE, such as that from rabbit lung, is... 

Vasodilating molecule(s) liberated from vascular endothelial cells in response to chemical substances (i.e., Acetylcholine, bradykinin, substance P, etc.) or mechanical stimuli (i.e., shear stress, transmural pressure, etc.). The EDRF includes NO, prostaglandin J2 (prostacyclin), and endothelium-derived hypeipolarizing factor (EDHF). 

The vascular endothelium plays an important role in regulation of vascular tone and permeability. Dilatation of arterioles to increase blood flow and constriction of endothelial cells of postcapillary venules causing exsudation of plasma constituents illustrates the complex nature of this cell type. Moreover, by expression of adhesion molecules and secretion of chemokines endothelial cells play an important role in the recruitment of leukocytes to the inflamed area. Endothelial cells express two basic types of adhesion molecules on their surface ... 

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... 

Peripheral Gl, vascular and bronchial smooth muscle, vascular endothelium, platelets Peripheral Smooth muscle of ileum, stomach fundus (rat), uterus, vasculature, endothelium Peripheral None identified Peripheral Post-ganglionic sympathetic neurons, sensory neurons Peripheral Cardiac muscle, post-ganglionic parasympathetic neurons (myenteric plexus), esophageal and vascular smooth muscle... 

Tissue plasminogen activator (alteplase t-PA) is a serine protease that is released into the circulation from vascular endothelium under conditions of injury or... 

Mu e, A., Elwell, J.H., Peterson, T.E., Hofmeyer, T.G., Heistad, D.D. and Harrison D.C. (1991). Chronic treatment with PEG-SOD partially restores endothelium dependent vascular relaxations in cholesterol fed rabbits. Circ. Res. 69, 1293-1300. 

Chin et al. (1992) have su ested that oxidized LDL and high-density lipoprotein (HDL) inactivate endothelial cell-derived NO. NO inactivation was due to the oxidized lipids within the lipoprotein particles and was thought to be explained by a chemical reaction between the lipoproteins and NO. Other investigators have shown that relaxation of vascular smooth muscle by acetylcholine or bradykinin (endothelium-dependent vasodilators) is inhibited by LDL (Andrews etal., 1987). The role of NO in the modification of LDL is discussed in full detail in Chapter 2. 

Moncada, S., Radomski, M.W. and Palmer, R.M. (1988). Endothelium-derived relaxing factor identification as nitric oxide and role in the control of vascular tone and platelet function. Biochem. Pharmacol. 37, 2495-2501. 

A relationship between polyol pathway activity and reduction in endothelium-dependent relaxation in aorta from chronic STZ-diabetic rats has recently been reported (Cameron and Cotter, 1992). In agreement with several previous studies (Oyama et al., 1986 Kamata et al., 1989), endothelial-dependent relaxation was defective in the diabetic rats but the deficit was prevented by prior treatment with an AR inhibitor. The mechanism underlying the defect has been speculated to be due to decreased production of endothelium-derived relaxing factor (EDRF) or nitric oxide, NO (Hattori et al., 1991). It has been speculated that these vascular abnormalities may lead to diminished blood flow in susceptible tissues and contribute to the development of some diabetic complications. NO is synthesized from the amino-acid L-arginine by a calcium-dependent NO synthase, which requires NADPH as a cofactor. Competition for NADPH from the polyol pathway would take place during times of sustained hyperglycaemia and... 

Lipid peroxides are directly cytotoxic to vascular endothelium... 

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