Vascular relaxation

Condensation of 594 with alloxan followed by methylation of the presumably formed purino[7,8-g]-6-azapteridine gave 597. Treatment of the latter with alkylamines afforded (87CPB4031) [1,2,4]triazino[2,3-/]purines 598. Compound 597 was active against P388 leukemia. Vascular relaxing effects of 598 were determined, but none showed potent activity (87CPB4031) (Scheme 123). 

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. 

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. 

Kowaluk, E. A., Fung, H-L., Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols. J. Pharmacol. Exp. Ther. 255 (1990),... 

Chung, S-J., Fung, H-L., Relationship between nitroglycerin-induced vascular relaxation and nitric oxide production. Probes with inhibitors and tolerance development. Biochem. Pharmacol. 45 (1993), p. 157-163... 

Labetalol appears to produce relaxation of vascular smooth muscle not only by a-blockade but also by a partial agonist effect at P2-receptors. In addition, labetalol may produce vascular relaxation by a direct non-receptor-mediated effect. 

E) Several halogenated hydrocarbons produce vascular relaxation to reduce blood pressure. 

Kots, A. Y., Skurat, A. V., Serienko, E. A., Bulargina, T. V., and Severin, E. S. (1992). Nitric oxide stimulates the cysteine-specific mono(ADP-ribosylation) of glyceralde-hyde-3-phosphate dehydrogenase from human. erythrocytes. FEBS Lett. 300, 9-12. Kowaluk, E. A., and Fung, H. L. (1990). Spontaneous liberation of nitric oxide cannot account for in vitro vascular relaxation by S-nitrosothiols. J. Pharmacol. Exp. Ther. 255,... 

Forstermann, U., Goppelt-Strube, M., Frolich, J. C., and Busse, R. (1986). Inhibitors of acylcoenzyme A Lysolecithin acyltransferase activate the production of endothelium-derived vascular relaxing factor. J. Pharmacol. Exp. Ther. 238, 352-359. 

A study has been undertaken to clarify whether glucocorticoid excess affects endothelium-dependent vascular relaxation in glucocorticoid treated patients and whether dexamethasone alters the production of hydrogen peroxide and the formation of peroxynitrite, a reactive molecule between nitric oxide and superoxide, in cultured human umbilical endothelial cells (7). Glucocorticoid excess impaired endothelium-dependent vascular relaxation in vivo and enhanced the production of reactive oxygen species to cause increased production of peroxynitrite in vitro. Glucocorticoid-induced reduction in nitric oxide availability may cause vascular endothelial dysfunction, leading to hypertension and atherosclerosis. 

Fumagalli F, Rossoni M, Iriti M, di Gennaro A, Faoro F, Borroni E, Borgo M, Scienza A, Sala A, Folco G. 2006. From field to health A simple way to increase the nutraceutical content of grape as shown by NO-dependent vascular relaxation. 

Mattagajasingh I, Kim CS, Naqvi A, Yamamori T, Hoffman TA, Jung SB, DeRicco J, Kasuno K, Irani K. 2007. SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci USA 104 14855-14860. 

Joy S, Siow RC, Rowlands DJ, Becker M, Wyatt AW, Aaronson PI, Coen CW, Kallo I, Jacob R, Mann GE. 2006. The isoflavone Equol mediates rapid vascular relaxation Ca2 + -independent activation of endothelial nitric-oxide synthase/Hsp90 involving ERK1/2 and Akt phosphorylation in human endothelial cells. J Biol Chem 281 27335-27345. 

Ruehlmann DO, Steinert JR, Valverde MA, Jacob R, Mann GE. 1998. Environmental estrogenic pollutants induce acute vascular relaxation by inhibiting L-type Ca2 + channels in smooth muscle cells. FASEB J 12 613-619. 

Tanaka Y, Yamaki F, Koike K, Toro L. New insights into the intracellular mechanisms by which PGI2 analogues elicit vascular relaxation cyclic AMP-independent, Gs-protein mediated-activation of MaxiK channel. Curr Med Chem Cardiovasc Hematol Agents. 2004 2 257-265. 

Has a beneficial effect on vascular relaxation in diabetes in rats [161]... 

The vasculature is composed of two principal cell layers, an endothelial cell lining the lumen and a surrounding layer of smooth muscle cells (SMC) (Figure 1). Vascular relaxation/contraction (vascular tone) is effected by relax-ation/contraction of the smooth muscle layer. In 1867, Brunton reported the use of amyl nitrite for the treatment of angina. Since that time, nitrovasodilators have been one of the most... 

Ricin caused vasodilatation and increased endothelial-dependent vascular relaxation resulting in hypotension. 

NO reacts with PUFAs to yield their respective nitroalkene derivatives that can be detected in plasma. These nitroalkene derivatives of various EFAs induce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, and have endogenous PPAR-y ligand activity... 

Abernethy DR, Babaoglu MO. Polymorphic variant of endothelial nitric oxide synthase (eNOS) markedly impairs endothelium-dependent vascular relaxation [abstract]. Clin Pharmacol Ther 2000 67 141. 

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