Search results for "NITRIC OXIDE SYNTHASE"
showing 10 items of 531 documents
Nitrergic modulation of gastrointestinal function during early endotoxemia.
2006
After bacterial infection, the host reacts by signalling to the central nervous system where a cascade of physiologic, neuroendocrine and behavioural processes is orchestrated, collectively termed the acute phase response. Endotoxemia following Gram-negative bacterial infection induces a wide array of effects, including fever, loss of appetite and changes in gastrointestinal function that attempt to eliminate the challenge and restore homeostasis. Systemic administration of low doses of endotoxin (5-40 microg/kg) to rats is associated with changes in gastrointestinal motor function, inhibition of gastric acid secretion and increase in the gastric mucosal resistance to damage. These changes …
Synthesis and inhibitory activity of dimethylamino-chalcone derivatives on the induction of nitric oxide synthase.
2002
A series of nine dimethylamino-chalcone derivatives (1,3-diaryl-propenones) was synthesized and screened as potential inhibitors of NO and PGE(2) production in the RAW 264.7 macrophage cell line. 4-Dimethylamino-2',5'-dimethoxychalcone (6) was found to be the most potent and dual inhibitor (IC(50s) in the submicromolar range) of NO and PGE(2) production. 2',6'-Dimethoxylation appeared to be an effective requirement for selective and potent inhibition of nitric oxide synthase induction as it was confirmed by Western blot analysis. Chalcone (6) at 25 mg kg(-1) by oral route, inhibited significantly the formation of oedema in the carrageenan-induced model of inflammation in mice.
Peroxynitrite generated from constitutive nitric oxide synthase mediates the early biochemical injury in short-term cultured hepatocytes
2000
AbstractEarly loss of P450 in rat hepatocyte cultures appears directly related to nitric oxide (NO) overproduction. This study provides experimental evidence for the induction – shortly after isolation through the classical procedure – of strong oxidative stress that involves both oxygen-derived and NO-derived species. NO formation at this stage is due to the early activation of liver constitutive NO synthase (cNOS). Immunodetection of nitrated proteins provides direct evidence of endogenous peroxynitrite (PN) formation upon hepatocyte isolation. On the basis of the combined use of dihydrorhodamine 123 and NOS inhibitors, the analysis of the amount, time course and nature of the species inv…
Involvement of nitric oxide in the mitochondrial action of efavirenz: a differential effect on neurons and glial cells
2014
Abstract The anti-human immunodeficiency virus (HIV) drug efavirenz (EFV) alters mitochondrial function in cultured neurons and glial cells. Nitric oxide (NO) is a mediator of mitochondrial dysfunction associated with HIV central nervous system symptoms. We show that EFV promotes inducible nitric oxide synthase (iNOS) expression in cultured glial cells and generated NO undermines their mitochondrial function, as inhibition of NOS partially reverses this effect. EFV inhibits mitochondrial Complex I in both neurons and glia; however, when the latter cells are treated for longer periods, other mitochondrial complexes are also affected in accordance with the increased NO production. These findi…
Artichoke, Cynarin and Cyanidin Downregulate the Expression of Inducible Nitric Oxide Synthase in Human Coronary Smooth Muscle Cells
2014
Artichoke (Cynara scolymus L.) is one of the world’s oldest medicinal plants with multiple health benefits. We have previously shown that artichoke leaf extracts and artichoke flavonoids upregulate the gene expression of endothelial-type nitric oxide synthase (eNOS) in human endothelial cells. Whereas NO produced by the eNOS is a vasoprotective molecule, NO derived from the inducible iNOS plays a pro-inflammatory role in the vasculature. The present study was aimed to investigate the effects of artichoke on iNOS expression in human coronary artery smooth muscle cells (HCASMC). Incubation of HCASMC with a cytokine mixture led to an induction of iNOS mRNA expression. This iNOS induction was c…
Role of nitric oxide and nitric oxide synthases in experimental models of denervation and reinnervation.
2001
Nitric oxide (NO) is a short-living free molecule synthesized by three different isoforms of nitric oxide synthases (NOS)—neuronal NOS, endothelial NOS, and inducible NOS—associated with neuromuscular transmission, muscle contractility, mitochondrial respiration, and carbohydrate metabolism in skeletal muscle. Neuronal NOS is constitutively expressed at the muscle fiber sarcolemma linked to the dystrophin-glycoprotein complex and concentrated at the neuromuscular endplate. There is increasing evidence that altered expression of neuronal NOS plays a role in muscle fiber damage in neuromuscular diseases such as dystrophinopathies and denervating disorders. Although there have been some previo…
Coexpression of inducible NO synthase and soluble guanylyl cyclase in colonic enterocytes: a pathophysiologic signaling pathway for the initiation of…
1998
Infectious diarrhea is often caused by the exotoxins of gram-negative bacteria such as Escherichia coli. However, these organisms also contain lipopolysaccharide (LPS) endotoxin. LPS induces nitric oxide synthase II (NOS II, inducible NOS) in various types of cells. We now demonstrate by RNase protection analysis, Western blot, and immunohistochemistry that the expression of NOS II mRNA and protein is markedly induced in colonic enterocytes of mice that ingest LPS with their drinking water. Using the same techniques, significant levels of soluble guanylyl cyclase (GC-S), the effector enzyme of NO, were found constitutively expressed in the mucosa. This creates a pathophysiologic autocrine p…
Myogenic NOS and endogenous NO production are defective in colon from dystrophic (mdx) mice
2001
The aim of the present study was to evaluate whether alterations in the distribution and/or function of nitric oxide synthase (NOS) could be involved in the development of the spontaneous mechanical tone observed in colon from dystrophic (mdx) mice. By recording the intraluminal pressure of isolated colon from normal mice, we showed that Nω-nitro-L-arginine methyl ester (L-NAME) increased the tone, even in the presence of tetrodotoxin. The effect was prevented by L-arginine, nifedipine, or Ca2+-free solution. In colon from mdx mice, L-NAME was ineffective. Immunohistochemistry revealed that the presence and distribution of neuronal (nNOS), endothelial, and inducible NOS isoforms in smooth m…
Therapeutic administration of 3,4,5-trimethoxy-4'-fluorochalcone, a selective inhibitor of iNOS expression, attenuates the development of adjuvant-in…
2003
We have previously investigated the effects of a series of dimethoxy- and trimethoxychalcone derivatives, with various patterns of fluorination, on nitric oxide production in LPS-stimulated murine RAW 264.7. The present study was designed to determine if 3,4,5-trimethoxy-4'-fluorochalcone (CH 17) could modulate the production of NO and/or prostaglandins in vivo. On the mouse macrophage cell line RAW 264.7 CH 17 inhibited dose-dependently NO production, with an IC(50) value in the nanomolar range, and reduced PGE(2) levels by a 58% at 10 microM. This compound had no direct inhibitory effect on iNOS and COX-2 activities. NO reduction was the consequence of inhibition of the expression of iNOS…
An antihypertensive lactoferrin hydrolysate inhibits angiotensin I-converting enzyme, modifies expression of hypertension-related genes and enhances …
2015
This study was aimed to explore whether an antihypertensive lactoferrin hydrolysate (LFH) can inhibit angiotensin I-converting enzyme (ACE) activity and modify the expression of genes related to hypertension in human umbilical vein endothelial cells (HUVEC). LFH induced significant inhibition of ACE activity but it did not affect ACE mRNA levels after 24 h of exposure. LFH treatment significantly affected the expression of genes encoding for proteins involved in nitric oxide pathway such as soluble guanylate cyclase 1 α3 subunit (GUCY1A3; 4.42-fold increase) and nitric oxide synthase trafficking (NOSTRIN; 2.45-fold decrease). Furthermore, expression of the PTGS2/COX-2 gene encoding prostagl…