Nitric oxide endothelium

Nitric oxide, endothelium-derived hyperpolarizing factor and prostaglandins Renal and cardiac fibrosis Glomerular function in the IPRK Disadvantages of the IPRK model Advantages of the IPRK model... 

Nitric oxide, endothelium-derived hyperpolarizing factor and prostaglandins... 

Endothelial Nitric Oxide Synthase (eNOS) Endothelin Converting Enzyme Endothelins Endothelium... 

Endothelium-derived relaxing factor (nitric oxide)... 

The results of a number of studies demonstrate that the gas nitric oxide (NO) plays a functional role in the central nervous system. This all originated with the discovery that the so-called endothelium-derived relaxing factor (EDRF), found in blood vessels, and thought to be a peptide, was in fact NO. The potential roles of this freely diffusible gas have subsequently been extended to many other tissues and organs but we will concentrate on the possible neuronal roles of what is obviously a novel mediator. There are also suggestions that the closely related carbon monoxide may also have a function in the central nervous system. 

Not all oxidants formed biolc cally have the potential to promote lipid peroxidation. The free radicals superoxide and nitric oxide [or endothelium-derived relaxing aor (EDRF)] are known to be formed in ww but are not able to initiate the peroxidation of lipids (Moncada et tU., 1991). The protonated form of the superoxide radical, the hydroperoxy radical, is capable of initiating lipid peroxidation but its low pili of 4.5 effectively precludes a major contribution under most physiological conditions, although this has been suggested (Aikens and Dix, 1991). Interestingly, the reaction product between nitric oxide and superoxide forms the powerful oxidant peroxynitrite (Equation 2.6) at a rate that is essentially difiiision controlled (Beckman eta/., 1990 Huie and Padmaja, 1993). 

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. 

Pique, J.M., Tepperman, B.L., Esplugues, J.V. and Whittle, B.J.R (1990). Involvement of endogenous nitric oxide, an endothelium-derived vasodilator, in the regulation of gastric mucosal blood flow. Gastroenterology 98, A196. 

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... 

Nitric oxide, a vasodilatory hormone released by the endothelium, is found in higher concentrations in HF patients and provides two main benefits in HF vasodilation and neurohormonal antagonism of endothelin.9 Nitric oxide s production is affected by the enzyme inducible nitric oxide synthetase (iNOS), which is up-regulated in the setting of HF, likely due to increased levels of angiotensin II, norepinephrine, and multiple cytokines. In HF, the physiologic response to nitric oxide appears to be blunted, which contributes to the imbalance between vasoconstriction and vasodilation. 

Hydroxyurea is a ribonucleotide reductase inhibitor that prevents DNA synthesis and traditionally has been used in chemotherapy regimens. Studies in the 1990s also found that hydroxyurea increases HbF levels as well as increasing the number of HbF-containing reticulocytes and intracellular HbF. Other beneficial effects of hydroxyurea include antioxidant properties, reduction of neutrophils and monocytes, increased intracellular water content leading to increased red cell deformability, decreased red cell adhesion to endothelium, and increased levels of nitric oxide, which is a regulator involved in physiologic disturbances.22... 

The endothelium has many diverse functions that enable it to participate in in-flammatoiy reactions (H27). These include modulation of vascular tone, and hence control of local blood flow changes in structure that allow leakage of fluids and plasma proteins into extravascular tissues local accumulation and subsequent extravasation into tissues of leukocytes and synthesis of surface molecules and soluble factors involved in leukocyte activation (B43). The endothelial cells themselves can modulate vascular tone by the release of vasoactive substances such as prostacyclin, nitric oxide (NO), ET. Endothelium-derived vasoactive substances... 

Results of a more recent series of investigations suggest that lead may cause hypertension in rats by increasing reactive oxygen species, which act as vasoconstrictors, and decreasing nitric oxide, a vasodilator released by the endothelium. The reactive oxygen species may be the hydroxyl radical, and did not appear to be the superoxide anion (Ding et al. 1998). 

The vascular endothelium produces a number of substances that are released basally into the blood vessel wall to alter vascular smooth muscle tone. One such substance is endothelin (ET-1). Endothelin exerts its effects throughout the body, causing vasoconstriction as well as positive inotropic and chronotropic effects on the heart. The resulting increases in TPR and CO contribute to an increase in MAP. Synthesis of endothelin appears to be enhanced by many stimuli, including Ag II, vasopressin, and the mechanical stress of blood flow on the endothelium. Synthesis is inhibited by vasodilator substances such as prostacyclin, nitric oxide, and atrial natriuretic peptide. There is evidence that endothelin is involved with the pathophysiology of many cardiovascular diseases, including hypertension, heart failure, and myocardial infarction. Endothelin receptor antagonists are currently available for research use only. 

First described in the 1980s as "endothelium-derived relaxing factor," nitric oxide (NO) is a vasodilator believed to play a role in regulation of blood pressure under physiologic and pathophysiological conditions. For example, inhibition of NO synthesis under normal conditions and during septic shock results in a significant elevation of blood pressure. 

L.J. Ignarro, G.M. Buga, K.S. Wood, R.E. Byrns, and G. Chaudhuri, Endothelium-derived relaxing factor produced and released from artery and vein is nitric-oxide. Proc. Natl. Acad. Sci. U.S.A. 84, 9265-9269 (1987). 

The aggregation of platelets contributes to the development of atherosclerosis and to the formation of acute thrombus. The activated platelets that adhere to the vascular endothelium generate lipid peroxides and oxygen free radicals, inhibiting the endothelial formation of prostacyclin and nitric oxide. 

The disturbance of balance between superoxide and nitric oxide occurs in a variety of common disease states. For example, altered endothelium-dependent vascular relaxation due to a decrease in NO formation has been shown in animal models of hypertension, diabetes, cigarette smoking, and heart failure [21]. Miller et al. [22] suggested that a chronic animal model atherosclerosis closely resembles the severity of atherosclerosis in patients. On the whole, the results obtained in humans, for example, in hypertensive patients [23] correspond well to animal experiments. It is important that endothelium-dependent vascular relaxation in patients may be improved by ascorbic acid probably through the reaction with superoxide. 

A deficiency in the local synthesis of vasodilating substances in the vascular endothelium, such as prostacyclin, bradykinin, and nitric oxide, or an increase in production of vasoconstricting substances such as angiotensin II and endothelin I ... 

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