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NO-synthase Inhibitor (no-synthase + inhibitor)
Selected AbstractsBalancing role of nitric oxide in complement-mediated activation of platelets from mCd59a and mCd59b double-knockout mice,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009Xuebin Qin CD59 is a membrane protein inhibitor of the membrane attack complex (MAC) of complement. mCd59 knockout mice reportedly exhibit hemolytic anemia and platelet activation. This phenotype is comparable to the human hemolytic anemia known as paroxysmal nocturnal hemoglobinuria (PNH), in which platelet activation and thrombosis play a critical pathogenic role. It has long been suspected but not formally demonstrated that both complement and nitric oxide (NO) contribute to PNH thrombosis. Using mCd59a and mCd59b double knockout mice (mCd59ab,/, mice) in complement sufficient (C3+/+) and deficient (C3,/,) backgrounds, we document that mCd59ab,/, platelets are sensitive to complement-mediated activation and provide evidence for possible in vivo platelet activation in mCd59ab,/, mice. Using a combination of L-NAME (a NO-synthase inhibitor) and NOC-18 or SNAP (NO-donors), we further demonstrate that NO regulates complement-mediated activation of platelets. These results indicate that the thrombotic diathesis of PNH patients could be due to a combination of increased complement-mediated platelet activation and reduced NO-bioavailability as a consequence of hemolysis. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Antiulcerogenic activity of crude ethanol extract and some fractions obtained from aerial parts of Artemisia annua L.PHYTOTHERAPY RESEARCH, Issue 8 2001Patrícia Corrêa Dias Abstract The resulting enriched sesquiterpene lactone fraction and the crude ethanol extract of Artemisia annua L. aerial parts, showed antiulcerogenic activity when administered orally, on the indomethacin induced ulcer in rats. The sesquiterpene lactone fraction yielded three different polarity fractions on column chromatography as follows: non-polar, medium polarity and polar fraction, When submitted to the same indomethacin-induced ulcer in rats they resulted in different levels of inhibition of the ulcerative lesion index. The participation of nitric oxide was evaluated on an ethanol-induced ulcer model which had a previous administration of L -NAME, a NO-synthase inhibitor. Under these conditions, the medium polarity fraction maintained the antiulcerogenic activity, suggesting that nitric oxide could not be involved in the antiulcerogenic activity. When the animal groups were treated with N-ethylmaleimide, an alkylator of sulphhydryl groups, using the same experimental model, the medium polarity fraction maintained its antiulcerogenic activity, suggesting that the pharmacological mechanism is not related to non-protein sulphydryl compounds. On the ethanol-induced ulcer with previous indomethacin treatment, the medium polarity fraction lost its antiulcerogenic activity indicating that the active compounds of Artemisia annua L. increase the prostaglandin levels in the gastric mucosa. This hypothesis was reinforced by an increase of adherent mucus production by the gastric mucosa, produced by the medium polarity fraction on the hypothermic restraint stress induced ulcer model. Copyright © 2001 John Wiley & Sons, Ltd. [source] Effect of anion channel blockers on l- arginine action in spermatozoa from asthenospermic menANDROLOGIA, Issue 2 2010S. Srivastava Summary In earlier studies, we have established that l- arginine enhances motility and metabolic rate in spermatozoa of goat, bull and mouse. In the present study this work was extended to human sperm cells obtained from the semen samples of asthenospermic patients, which are characterised by low motility. The metabolic rate was followed by monitoring the glucose consumption (1- 13C glucose as substrate) and the production of lactate in sperm cells, using 13C NMR. The stimulatory effect of l- arginine was neutralised on adding an NO-synthase inhibitor like N, -nitro- l- arginine methyl ester. On the other hand, the inactive d -enantiomorph did not affect the stimulatory effect of l- arginine. This strongly suggests that l- arginine acts through the NO signal pathway. We also demonstrated that the stimulatory effect of l- arginine was inhibited in the presence of anion channel inhibitors like 4-acetamido-4,-isothiocyanostilbene-2,2,-disulphonic acid, 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone. Furthermore, bicarbonate supplementation was found to be essential for the action of l- arginine. These observations indicate that l- arginine induces NO synthesis and stimulates motility and metabolism only when an active anion transport system is present. [source] Characterization of endothelial factors involved in the vasodilatory effect of simvastatin in aorta and small mesenteric artery of the ratBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2000Maria Álvarez De Sotomayor Vascular effects of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, were studied in conductance (aorta) and resistance vessels (branch II or III of superior mesenteric artery, SMA) of the rat (12,14 weeks old). Simvastatin produced relaxation of both aorta and SMA, with and without functional endothelium. These responses were inhibited by the product of HMG-CoA reductase, mevalonate (1 mmol l,1). In vessels with functional endothelium, the NO-synthase inhibitor, L -NG -nitroarginine (L -NOARG, 30 ,mol l,1), inhibited simvastatin-induced relaxation. In the presence of L -NOARG, relaxation to simvastatin was lower in vessels with endothelium than in endothelium-denuded arteries without L -NOARG. The cyclo-oxygenase inhibitor, indomethacin (10 ,mol l,1), abolished endothelium-dependent component of the response to simvastatin in both arteries. The combination of L -NOARG plus indomethacin did not produce further inhibition. The Tp receptor antagonist, GR 32191B (3 ,mol l,1), did not affect relaxation in aorta but it reduced response to low concentrations of simvastatin in SMA. However, the inhibitory effect of L -NOARG was less marked in the presence of GR 32191B in aorta but not in SMA. The endothelium-dependent relaxation to simvastatin was inhibited by the superoxide dismutase (SOD, 100 u ml,1) or by the tyrosine kinase inhibitor, genistein (30 ,mol l,1) in the two arteries. The present study shows that simvastatin produces relaxation of conductance and small arteries through mevalonate-sensitive pathway. The endothelium-dependent relaxation to simvastatin involves both NO and vasodilator eicosanoids by a mechanism sensitive to SOD, and to genistein. Also, the results highlighted participation in the aorta of endothelial vasoconstrictor eicosanoids acting on the Tp receptor after blockage of NO synthase only. British Journal of Pharmacology (2000) 131, 1179,1187; doi:10.1038/sj.bjp.0703668 [source] Nitric oxide-dependent protein synthesis in parotid and submandibular glands of anaesthetized rats upon sympathetic stimulation or isoprenaline administrationEXPERIMENTAL PHYSIOLOGY, Issue 2 2004Shariel Sayardoust In anaesthetized female rats, the ,-adrenoceptor agonist isoprenaline was intravenously infused (20 ,g kg,1 min,1) for 30 min or the ascending cervical sympathetic nerve trunk was intermittently stimulated (50 Hz, 1 s every tenth second) on one side for 30 min. The incorporation of [3H]leucine into trichloroacetic acid (TCA)-insoluble material was used as an index of protein synthesis. In response to isoprenaline, the [3H]leucine incorporation increased by 79% in the parotid glands and by 82% in the submandibular glands. The neuronal type NO-synthase inhibitor N-PLA, reduced (P < 0.001) this response to 26% and 20%, respectively. Sympathetic stimulation under ,-adrenoceptor blockade increased the [3H]leucine incorporation by 192% in the parotid glands and by 35% in the submandibular glands. N-PLA reduced the corresponding percentage figures to 86% (P < 0.01) and 8% (P < 0.05). When tested in the parotid glands, the non-selective NO-synthase inhibitor L -NAME reduced (P < 0.01) the nerve-evoked response to 91%. The increase in [3H]leucine incorporation in response to sympathetic stimulation under ,-adrenoceptor blockade was not affected by N-PLA in the parotid (139%versus 144%) and submandibular glands (39%versus 34%). In non-stimulated glands, the [3H]leucine incorporation was not influenced by the NO-synthase inhibitors. In conclusion, ,-adrenoceptor mediated salivary gland protein synthesis is largely dependent on NO generation by neuronal type NO-synthase, most likely of parenchymal origin. 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