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Nitric Oxide Synthesis (nitric + oxide_synthesis)
Selected AbstractsNitric oxide synthesis and nitric oxide synthase expression in the kidney of rats treated by FK506NEPHROLOGY, Issue 1 2002LiMing WANG SUMMARY: FK506-induced nephrotoxicity is characterized by a disturbance in renal haemody-namics that is attributed to an imbalance between the various modulators of renal vascular tone. It has not been well defined whether nitric oxide (NO), as an important vasoactive factor, is involved in FK506-induced nephrotoxicity. This study was designed to evaluate the involvement of nitric oxide in FK506-induced nephrotoxicity by investigating NO synthesis and NO synthase (NOS) expression in the kidney of rats treated with FK506. Male Wistar rats weighing 240,260 g, aged 11 weeks, were administered with FK506 (3.2mg/kg per day i.m.) for 4 weeks. Renal function and urinary NOx was measured using biochemical methods at the end of both 2 and 4 weeks of treatment. Expression of NOS protein and NOS mRNA in the kidney was also investigated using Western blot analysis and reverse transcription/polymerase chain reaction, respectively. FK506 administration induced nephrotoxicity, which was indicated by renal dysfunction (elevated blood urea nitrogen and creatinine, and reduced creatinine clearance, P < 0.05 vs control). FK506-induced nephrotoxicity was accompanied by higher urinary NOx excretion at the end of 2 weeks' treatment. In parallel with an increase in NO synthesis, increased eNOS protein and mRNA expression were also found in the renal medulla and renal cortex at week 2. the expression remained at higher levels in the renal medulla and returned to normal levels in the renal cortex at week 4. FK506 treatment induced nephrotoxicity in rats, which was accompanied by a temporal increase in NO synthesis in the kidney. Increased eNOS protein and mRNA expression were also found in the kidney of treated rats, which may be responsible for the enhanced NO synthesis. [source] Nitric oxide synthesis and signalling in plantsPLANT CELL & ENVIRONMENT, Issue 5 2008IAN D. WILSON ABSTRACT As with all organisms, plants must respond to a plethora of external environmental cues. Individual plant cells must also perceive and respond to a wide range of internal signals. It is now well-accepted that nitric oxide (NO) is a component of the repertoire of signals that a plant uses to both thrive and survive. Recent experimental data have shown, or at least implicated, the involvement of NO in reproductive processes, control of development and in the regulation of physiological responses such as stomatal closure. However, although studies concerning NO synthesis and signalling in animals are well-advanced, in plants there are still fundamental questions concerning how NO is produced and used that need to be answered. For example, there is a range of potential NO-generating enzymes in plants, but no obvious plant nitric oxide synthase (NOS) homolog has yet been identified. Some studies have shown the importance of NOS-like enzymes in mediating NO responses in plants, while other studies suggest that the enzyme nitrate reductase (NR) is more important. Still, more published work suggests the involvement of completely different enzymes in plant NO synthesis. Similarly, it is not always clear how NO mediates its responses. Although it appears that in plants, as in animals, NO can lead to an increase in the signal cGMP which leads to altered ion channel activity and gene expression, it is not understood how this actually occurs. NO is a relatively reactive compound, and it is not always easy to study. Furthermore, its biological activity needs to be considered in conjunction with that of other compounds such as reactive oxygen species (ROS) which can have a profound effect on both its accumulation and function. In this paper, we will review the present understanding of how NO is produced in plants, how it is removed when its signal is no longer required and how it may be both perceived and acted upon. [source] Changes in reactivity of rat arteries subjected to dynamic stretchACTA PHYSIOLOGICA, Issue 1 2000Dvoretsky The effect of dynamic stretch on the reactivity of the rat tail and mesenteric artery segments was studied. Segments mounted on a myograph were stretched by a computer-controlled motorized micromanipulator. Dynamic stretch (1, 5 or 7 Hz) inhibited the artery constriction induced by noradrenaline (10 ,M), 5-hydroxytryptamine (0.7 ,M), or electrical field stimulation of intramural nerves. In contrast, dynamic stretch enhanced the tetrodotoxin-insensitive dilation induced by electrical field stimulation of noradrenaline-contracted arteries. Maximal increase of dilation evoked by electrical field stimulation (24.5 ± 5.0% in mesenteric and 50.3 ± 15.6% in the tail artery) was observed at a dynamic stretch-frequency of 5 Hz. An inhibitor of nitric oxide synthesis, NG -nitro- L -arginine (100 ,M), abolished the difference in reactivity between static and dynamic conditions. The results indicate that dynamic stretch of the arteries activates nitric oxide synthesis/secretion, thus reducing constrictor and increasing dilator responses to the stimuli used. [source] Extra-nuclear signaling of estrogen receptorsIUBMB LIFE, Issue 8 2008Xiao-Dong Fu Abstract Estrogen controls multiple biological functions through binding to estrogen receptors (ERs). Traditionally, ERs have been regarded as transcription factors regulating the expression of target genes. However, growing evidence of rapid estrogen's actions in a number of tissues has been accumulating and alternative mechanisms of signal transduction have been proposed. These so called "extra-nuclear actions" do not require gene expression or protein synthesis and are independent of the nuclear localization of ERs. Indeed, some of these actions are elicited by ERs residing at or near the plasma membrane. Membrane-associated molecules such as ion channels, G proteins, the tyrosine kinase c-Src as well as growth factor receptors are modulated by liganded ERs within the membrane, leading to the activation of downstream cascades such as mitogen-activated protein kinase, phosphatidylinositol 3-OH kinase, protein kinase A, and protein kinase C. These cascades mediate some important rapid actions of estrogen, such as the activation of nitric oxide synthesis or the remodeling of actin cytoskeleton. In addition, these pathways are critical for the regulation of the expression of a number of target proteins implicated in cell proliferation, apoptosis, differentiation, movement, and homeostasis. In this manner, the extra-nuclear pathways are tightly integrated with the genomic pathways to orchestrate the full spectrum of estrogen's biological functions. The recent advancements in the characterization of the molecular basis of the extra-nuclear signaling of estrogen helps to understand the role of estrogen on human cells, and may in future turn out to be of relevance for clinical purposes. © 2008 IUBMB IUBMB Life, 60(8): 502,510, 2008 [source] Beneficial effect of enalapril in spontaneously hypertensive rats cardiac remodeling with nitric oxide synthesis blockadeJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2002R. L. de Andrade Zorzi Abstract Aims. To study the efficiency of an angiotensin converting enzyme inhibitor on the blood pressure (BP) and the myocardium remodeling when spontaneously hypertensive rats (SHRs) are submitted to nitric oxide synthesis (NOs) blockade (with L-NAME) and simultaneously treated. Methods. Young adult male SHRs were separated in four groups (n = 5) and treated for 20 days: Control, L-NAME, L-NAME+Enalapril, and Enalapril. The alterations of the BP, heart mass/body mass ratio and stereological parameters for myocytes, connective tissue and intramyocardial vessels were studied among the groups. Results. The SHRs with NOs blockade showed a great modification of the myocardium with extensive areas of reparative and interstitial fibrosis and accentuated hypertrophy of the cardiac myocytes (cross sectional area 60% higher in animals taking L-NAME than in Control SHRs). Comparing the SHRs with NO deficiency (L-NAME group), the Control SHRs and the Enalapril treated SHRs significant differences were found in the BP and in all stereological parameters. The NO deficiency caused an important BP increment in SHRs that was partially attenuated by Enalapril. This Enalapril effect was more pronounced in Control SHRs. A significant increment of the intramyocardial vessels was observed in NO deficient SHRs and Control SHRs treated with Enalapril demonstrated by the stereology (greater microvascular densities in treated SHRs). Conclusion. Enalapril administration showed a beneficial effect on vascular remodeling and myocardial hypertrophy in SHRs. In SHRs with NO blockade, however, the beneficial effect of Enalapril occurred only in vascular remodeling. [source] Blockade of NMDA receptors and nitric oxide synthesis in the dorsolateral periaqueductal gray attenuates behavioral and cellular responses of rats exposed to a live predatorJOURNAL OF NEUROSCIENCE RESEARCH, Issue 11 2009Daniele Cristina Aguiar Abstract Innate fear stimulus induces activation of neurons containing the neuronal nitric oxide synthase enzyme (nNOS) in defensive-related brain regions such as the dorsolateral periaqueductal gray (dlPAG). Intra-dlPAG administration of nitric oxide synthase (NOS) inhibitors and glutamate antagonists induce anxiolytic-like responses. We investigated the involvement of nitric oxide (NO) and glutamate neurotransmission in defensive reactions modulated by dlPAG. We tested if intra-dlPAG injections of the selective nNOS inhibitor, N-propyl- L -arginine (NP), or the glutamate antagonist, AP7 (2-amino-7-phosphonoheptanoic acid), would attenuate behavioral responses and cellular activation induced by predator exposure (cat). Fos-like immunoreactivity (FLI) was used as a marker of neuronal functional activation, whereas nNOS immunohistochemistry was used to identify NOS neurons. Cat exposure induced fear responses and an increase of FLI in the dlPAG and dorsal premammillary nucleus (PMd). NP and AP7 attenuated the cat-induced behavioral responses. Whereas NP tended to attenuate FLI in the dlPAG, AP7 induced a significant reduction in cellular activation of this region. The latter drug, however, increased FLI and double-labeled cells in the PMd. Cellular activation of this region was significantly correlated with time spent near the cat (r = 0.7597 and 0.6057 for FLI and double-labeled cells). These results suggest that glutamate/NO-mediated neurotransmission in the dlPAG plays an important role in responses elicit by predator exposure. Blocking these neurotransmitter systems in this brain area impairs defensive responses. The longer time spent near the predator that follows AP7 effect could lead to an increased cellular activation of the PMd, a more rostral brain area that has also been related to defensive responses. © 2009 Wiley-Liss, Inc. [source] Localization and changes of intraneural inflammatory cytokines and inducible-nitric oxide induced by mechanical compressionJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2005Shigeru Kobayashi Abstract Study design: Investigation of intraneural inflammation induced by mechanical compression. Objectives: In order to investigate the mechanism of neuropathy, this study used a median nerve compression model in dogs. Immunohistochemistry was used to examine the localization and changes of inflammatory cytokines and nitric oxide (NO). Summary of background data: The manifestation of pain at sites of inflammation has a close relationship with the release of mediators from macrophages such as interleulin-1 (IL-1) and tumor necrosis factor-, (TNF-,), as well as with NO. However, the mediators involved in inflammation of nerve due to mechanical compression remain almost unknown. Methods: In this study, the median nerve of dogs was compressed with a clip for three weeks to observe the changes caused by compression. Immunohistochemistry was done by the avidin-biotin-peroxidase complex method to observe the changes of T cells (CD45) and macrophages (Mac-1) after compression. Antibodies against IL-,, TNF-,, and inducible nitric oxide synthesis (i-NOS) were used to examine the localization and changes of these mediators caused by nerve compression. Results: In control animals, resident T cells were detected, but there were no macrophages. IL-1, was positive in the Schwann cells and vascular endothelial cells. However, no cells showed TNF-, or i-NOS positively. After nerve compression, numerous T cells and macrophages appeared among the demyelinized nerve fibers. The macrophages were positive for IL-1,, TNF-, and i-NOS. Conclusion: Inflammatory cytokines and NO may be involved in intraneural inflammatory changes arising from mechanical compression. Such mediators may be of importance in the manifestation of neuropathy. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Spontaneous labor increases nitric oxide synthesis during the early neonatal periodPEDIATRICS INTERNATIONAL, Issue 4 2001Akihiko Endo AbstractBackground: This paper aimed to assess the influence of spontaneous labor upon endogenous nitric oxide (NO) and endothelin 1 (ET-1) during transition to extrauterine life. Methods: The serum levels of NO metabolites (the sum of nitrites and nitrates (NOx)) and the plasma level of ET-1 were determined in 53 healthy full-term infants (spontaneous labor group; n=40, cesarean delivery group; n=13). In both groups, blood samples were obtained from a cord vein at birth and from a peripheral vein at 5 days of age. Results: The differences in serum NOx concentrations between the spontaneous labor group and the elective cesarean group were not significant at birth. By the age of 5 days, serum NOx concentrations had risen significantly in the spontaneous labor group to become significantly higher in the elective cesarean group. Conclusion: It is speculated that spontaneous labor might enhance endogenous NO synthesis at 5 days of age. [source] Thymoquinone supplementation attenuates hypertension and renal damage in nitric oxide deficient hypertensive ratsPHYTOTHERAPY RESEARCH, Issue 5 2007Mahmoud M. Khattab Abstract The present study was undertaken to evaluate the protective effect of thymoquinone (TQ), the main constituent of the volatile oil from Nigellasativa seeds, in rats after chronic inhibition of nitric oxide synthesis with N, -nitro- l -arginine methyl esters (l -NAME). Rats were divided randomly into different treatment groups: control, l -NAME, TQ and l -NAME + TQ. Hypertension was induced by 4 weeks administration of l -NAME (50 mg/kg/day p.o.). TQ was administered alone or in combination with l -NAME and continued for 4 weeks. The animals were killed, and the serum and kidney tissues were isolated for the determination of creatinine and glutathione (GSH), respectively. Rats receiving l -NAME showed a progressive increase in systolic blood pressure compared with control rats. Concomitant treatment with TQ (0.5 and 1 mg/kg/day p.o.) reduced the increase in systolic blood pressure induced by l -NAME in a dose dependent manner. Kidney injury was demonstrated by a significant increase in serum creatinine and a decrease in GSH in kidney tissue from l -NAME treated rats. Treatment of rats with TQ decreased the elevated creatinine and increased GSH to normal levels. TQ inhibited the in vitro production of superoxide radical in enzymatic and non-enzymatic systems. In conclusion, TQ is effective in protecting rats against l -NAME-induced hypertension and renal damage possibly via antioxidant activity. Copyright © 2007 John Wiley & Sons, Ltd. [source] Butanolides from Machilus thunbergii and their inhibitory activity on nitric oxide synthesis in activated macrophagesPHYTOTHERAPY RESEARCH, Issue 4 2003Nam Yi Kim Abstract In activated macrophages the inducible form of nitric oxide synthase (iNOS) generates high amounts of the toxic mediator, nitric oxide (NO), that contributes to the circulatory failure associated with septic shock. Three butanolides were isolated from Machilus thunbergii as active principles which inhibit the production of NO in lipopolysaccharide-activated RAW 264.7 cells, and their structures were identi,ed as litsenolide A2 (1), B1 (2) and B2 (3). They showed dose-dependent inhibition of NO syntheses and the IC50s were 3.36, 3.70 and 6.19 µm, respectively. These new inhibitors of iNOS may have potential in the treatment of endotoxaemia and in,ammation accompanied by the overproduction of NO. Copyright © 2003 John Wiley & Sons, Ltd. [source] Spongy Polyethersulfone Membrane for Hepatocyte Cultivation: Studies on Human Hepatoma C3A CellsARTIFICIAL ORGANS, Issue 9 2008Andrzej Kinasiewicz Abstract:, There are different types of membranes used for hepatocyte cultivation. In our studies, spongy polyethersulfone (PES) membranes were examined as a support for hepatic cell cultivation in vitro. The extended surface of the membranes allows to introduce a high cell number especially in three-dimensional gel structure. Scanning electron microscopy analysis indicated that C3A cells used in our experiments grew well on PES membranes forming microvilli characteristic for normal hepatocytes. Analysis of cell viability proved that spongy PES membrane is well tolerated by J774 macrophages and did not stimulate nitric oxide synthesis. Bile canalicular structures were observed in fluorescence microscopy after F-actin staining with tetramethyl rhodamine iso-thiocyanate (TRITC)-phalloidin. The C3A cells showed high affinity to the PES membranes and adhered to almost 90% during the initial 24 h of incubation. Albumin production increased during static culture from the value of 805.2 ± 284.4 (ng/24 h/initial 106 cells) during the first days, to 2017.6 ± 505.9 (ng/24 h/initial 106 cells) after 10 days of culture. In conclusion, the spongy PES membranes can be used as scaffold for hepatocyte cultivation, especially for the creation of three-dimensional environments. [source] Control of non-adrenergic non-cholinergic reflex motor responses in circular muscle of guinea-pig small intestine by Met-enkephalinAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2002Chr. Ivancheva Summary 1 A triple organ bath method allowing the synchronous recording of the motor activity of the circular muscle layer belonging to the oral and anal segments of guinea-pig small intestine adjacent to an electrically stimulated middle segment was developed to study the ascending and descending reflex motor responses. 2 Electrical field stimulation (0.8 ms, 40 V, 5 Hz, 10 s) applied to the middle part of the segments elicited tetrodotoxin (1 ,m)-sensitive ascending and descending contractile responses of the nonstimulated parts, oral and anal, respectively. The ascending contraction was more pronounced as compared with the descending contraction. 3 In the presence of phentolamine (5 ,m), propranolol (5 ,m) and atropine (3 ,m) a significant decrease in the amplitude of the ascending contraction was seen and a descending relaxation, instead of a contraction was observed. 4 Met-enkephalin applied at a single concentration (0.1 ,m) or cumulatively (0.001,1 ,m) inhibited both non-adrenergic non-cholinergic (NANC) descending relaxation and ascending contraction with similar efficacy but different potency, IC50 being 5.9 ± 0.3 and 39.0 ± 4 nm, respectively. Naloxone (0.5 ,m) prevented the effects of Met-enkephalin. 5 L-NNA (0.5 mm), an inhibitor of nitric oxide synthesis, increased the ascending contraction and strongly reduced but not abolished the descending relaxation. l -Arginine (0.5 mm) restored the motor responses to the initial level in l -NNA-pretreated preparations, d -Arginine (0.5 nm) had no effects. 6 Met-enkephalin (0.1 ,m) depressed the l -NNA-dependent increase of the ascending contraction and failed to change the l -NNA-resistant part of the descending relaxation. 7 Met-enkephalin did not alter spontaneous NANC mechanical activity. SNP (1 or 10 ,m), an exogenous donor of nitric oxide, caused a concentration-dependent relaxation. The effects of SNP persisted in Met-enkephalin (0.1 ,m)-pretreated preparations. 8 NANC reflex ascending contraction and descending relaxation were synchronously induced by a local nerve stimulation indicating a functional coactivation of NANC orally projected excitatory and anally directed inhibitory pathways. Acting prejunctionally, Met-enkephalin provided a negative controlling mechanism inhibiting both ascending and descending, mainly nitric oxide mediated, reflex responses. A higher sensitivity of the descending relaxation to Met-enkephalin was observed suggesting an essential role of opioid(s) in reducing the efficacy of descending motor activity. [source] Electrophysiological and Neurochemical Evidence for Voltage-Dependent Ca2+ Channel Blockade by a Novel Neuroprotective Agent NS-7,BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2001Michiko Oka In rat dorsal root ganglion neurones, NS-7 (0.3,100 ,M) inhibited the whole-cell Ba2+ currents (IBa) in a voltage-dependent manner, in which the compound more potently blocked the IBa elicited from the holding potential of ,40 mV than that induced from ,80 mV. In slices of rat cerebral cortex, KCl-evoked nitric oxide synthesis was markedly inhibited by ,-conotoxin GVIA and ,-agatoxin IVA, but only slightly attenuated by nifedipine, suggesting that the response is mediated predominantly through activation of N-type and P/Q-type Ca2+ channels. NS-7 (1,100 ,M) inhibited the KCl-stimulated nitric oxide synthesis in a manner dependent on the intensity of the depolarizing stimuli. Moreover, weak but significant inhibitory effect of NS-7 was observed even after wash-out. Similar voltage-dependent inhibition of the KCl response was observed by a limited concentration (10 ,M) of verapamil. These findings indicate that NS-7 in several concentrations blocks Ca2+ channel in a voltage-dependent manner. [source] RELAXANT EFFECT OF ADRENOMEDULLIN ON BOVINE ISOLATED IRIS SPHINCTER MUSCLE UNDER RESTING CONDITIONSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2005Y Uchikawa SUMMARY 1.,The mechanisms involved in the fine adjustment of iris sphincter muscle tone are largely unknown. The aim of the present study was to clarify the effects of adrenomedullin on the resting tension of the bovine isolated iris sphincter muscle. 2.,The motor activity of the bovine isolated iris sphincter muscle was measured isometrically. The effects of adrenomedullin on resting tension were analysed in the presence of indomethacin. The presence of adrenomedullin mRNA in the preparation was determined by reverse transcription,polymerase chain reaction. Immunolabelling for adrenomedullin was also performed. 3.,Adrenomedullin significantly decreased the resting tension of the muscle. The relaxant effect of adrenomedullin was significantly inhibited by adrenomedullin (22,52), a putative antagonist for the adrenomedullin receptor, or calcitonin gene-related peptide (CGRP) (8,37), a putative antagonist for the CGRP1 receptor. The relaxant effect was almost completely blocked by a combination of adrenomedullin (22,52) and CGRP (8,37). 4.,The relaxant effect of adrenomedullin was also significantly diminished by 2,,5,-dideoxyadenosine, an inhibitor of adenylate cyclase, NG -nitro- l -arginine, an inhibitor of nitric oxide synthesis, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase. 5.,Reverse transcription,polymerase chain reaction analysis showed that adrenomedullin mRNA was expressed in the muscle strip. Immunopositive staining for adrenomedullin was detected in blood vessel cells and in the iris sphincter muscle cells. 6.,These results suggest that adrenomedullin may be an autocrine and paracrine regulator of the resting tension of the iris sphincter muscle. Its biological effects may be due to the direct involvement of adrenomedullin receptors and also to the stimulation of CGRP1 receptors. The stimulation of these receptors by the peptide leads to the activation of adenylate cyclase and soluble guanylate cyclase and subsequent relaxation of the muscle strip. [source] | |||||||||||||