Effect of nitric oxide synthase inhibitors on basal microvessel permeability and endothelial cell [Ca2+]i

1997 ◽  
Vol 273 (2) ◽  
pp. H747-H755 ◽  
Author(s):  
P. He ◽  
M. Zeng ◽  
F. E. Curry
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Transient Increase ◽  
Deferoxamine Mesylate ◽  
Activated State ◽  
Nos Inhibitors ◽  
Microvessel Permeability ◽  
The Mean ◽  
Oxide Synthase

We evaluated the role of basal nitric oxide (NO) release in the regulation of microvessel permeability under resting conditions. We measured changes in microvessel hydraulic conductivity (Lp) and endothelial cytoplasmic calcium concentration ([Ca2+]i) after application of NO synthase (NOS) inhibitors to the lumen of individually perfused frog mesenteric venular microvessels. NOS inhibitors caused a transient increase in Lp. The mean ratios of peak test Lp values relative to control values in the presence of N omega-nitro-L-arginine methyl ester (L-NAME) at concentrations of 1, 10, and 100 microM were 2.5 +/- 0.6, 2.9 +/- 0.7, and 4.8 +/- 0.4, respectively. N omega-monomethyl-L-arginine (L-NMMA) showed a similar effect and a biologically inactive isomer of L-NMMA, D-NMMA, showed no effect. These results demonstrate that basal levels of NO play a role in modulating microvessel permeability different from that due to NO produced in response to inflammatory agents. In the activated state NOS inhibitors attenuated the increased microvessel permeability in response to ionomycin and ATP [P. He, B. Liu, and F. E. Curry. Am. J. Physiol. 272 (Heart Circ. Physiol. 41): H176-H185, 1997]. The transient increase in basal permeability induced by NOS inhibitors was not accompanied by an increase in endothelial cell [Ca2+]i and did not require the presence of extracellular calcium. Application of ketotifen, a mast cell stabilizer, and an iron-chelating reagent, deferoxamine mesylate, attenuated the transient increase in Lp induced by L-NMMA, suggesting that basal NO may have an important antioxidant role in regulating normal permeability.

scholarly journals The Role of Neuronal Nitric Oxide Synthase in Regulation of Cerebral Blood Flow in Normocapnia and Hypercapnia in Rats

1995 ◽  
Vol 15 (5) ◽  
pp. 774-778 ◽  
Author(s):  
Qiong Wang ◽  
Dale A. Pelligrino ◽  
Verna L. Baughman ◽  
Heidi M. Koenig ◽  
Ronald F. Albrecht
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Inhibitory Action ◽  
Neuronal Nitric Oxide Synthase ◽  
Muscarinic Agonist ◽  
Doppler Flowmetry ◽  
Nos Inhibitors ◽  
Oxide Synthase

The nitric oxide synthase (NOS) inhibitors, nitro-L-arginine, its methyl ester, and N-monomethyl-L-arginine, have been shown to attenuate resting CBF and hypercapnia-induced cerebrovasodilation. Those agents nonspecifically inhibit the endothelial and neuronal NOS (eNOS and nNOS). In the present study, we used a novel nNOS inhibitor, 7-nitroindazole (7-NI) to examine the role of nNOS in CBF during normocapnia and hypercapnia in fentanyl/N2O-anesthetized rats. CBF was monitored using laser-Doppler flowmetry. Administration of 7-NI (80 mg kg−1 i.p.) reduced cortical brain NOS activity by 57%, the resting CBF by 19–27%, and the CBF response to hypercapnia by 60%. The 60% reduction was similar in magnitude to the CBF reductions observed in previous studies in which nonspecific NOS inhibitors were used. In the present study, 7-NI did not increase the MABP. Furthermore, the CBF response to oxotremorine, a blood–brain barrier permeant muscarinic agonist that induces cerebrovasodilation via endothelium-derived NO, was unaffected by 7-NI. These results confirmed that 7-NI does not influence eNOS; they also indicated that the effects of 7-NI on the resting CBF and on the CBF response to hypercapnia in this study were solely related to its inhibitory action on nNOS. The results further suggest that the NO synthesized by the action of nNOS participates in regulation of basal CBF and is the major, if not the only, category of NO contributing to the hypercapnic CBF response.

scholarly journals Role of Endothelial Nitric Oxide Synthase in Endothelial Cell Migration

1999 ◽  
Vol 19 (5) ◽  
pp. 1156-1161 ◽  
Author(s):  
Toyoaki Murohara ◽  
Bernhard Witzenbichler ◽  
Ioakim Spyridopoulos ◽  
Takayuki Asahara ◽  
Bo Ding ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Endothelial Cell Migration ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Prelimbic neuronal nitric oxide synthase inhibition exerts antidepressant-like effects independently of BDNF signalling cascades

2019 ◽  
Vol 31 (03) ◽  
pp. 143-150 ◽  
Author(s):  
Vitor Silva Pereira ◽  
Angélica C.D. Romano Suavinha ◽  
Gregers Wegener ◽  
Sâmia R.L. Joca
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Treatment Options ◽  
Nmda Antagonists ◽  
Systemic Injection ◽  
Behavioural Effects ◽  
Nos Inhibitors ◽  
Oxide Synthase ◽  
Mtor Signalling

AbstractObjectivesNMDA antagonists and nitric oxide synthase (NOS) inhibitors induce antidepressant-like effects and may represent treatment options for depression. The behavioural effects of NMDA antagonists seem to depend on Tyrosine kinase B receptor (TrkB) activation by BDNF and on mechanistic target of rapamycin (mTOR), in the medial prefrontal cortex (mPFC). However, it is unknown whether similar mechanisms are involved in the behavioural effects of NOS inhibitors. Therefore, this work aimed at determining the role of TrkB and mTOR signalling in the prelimbic area of the ventral mPFC (vmPFC-PL) in the antidepressant-like effect of NOS inhibitors.MethodsPharmacological treatment with LY235959 or ketamine (NMDA antagonists), NPA or 7-NI (NOS inhibitors), BDNF, K252a (Trk antagonist) and rapamycin (mTOR inhibitor) injected systemically or into vmPFC-PL followed by behavioural assessment.ResultsWe found that bilateral injection of BDNF into the vmPFC-PL induced an antidepressant-like effect, which was blocked by pretreatment with K252a and rapamycin. Microinjection of LY 235959 into the vmPFC-PL induced antidepressant-like effect that was suppressed by local rapamycin but not by K252a pretreatment. Microinjection of NPA induced an antidepressant-like effect insensitive to both K252a and rapamycin. Similarly, the antidepressant-like effects of a systemic injection of ketamine or 7-NI were not affected by blockade of mTOR or Trk receptors in the vmPFC-PL.ConclusionOur data support the hypothesis that NMDA blockade induces an antidepressant-like effect that requires mTOR but not Trk signalling into the vmPFC-PL. The antidepressant-like effect induced by local NOS inhibition is independent on both Trk and mTOR signalling in the vmPFC-PL.

Nitric oxide, ischaemia and brain inflammation

2007 ◽  
Vol 35 (5) ◽  
pp. 1133-1137 ◽  
Author(s):  
S. Murphy ◽  
C.L. Gibson
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cerebral Ischaemia ◽  
Brain Inflammation ◽  
Experimental Stroke ◽  
Nitric Oxide Donors ◽  
Nos Inhibitors ◽  
Oxide Synthase ◽  
Inducible Nos

Cerebral ischaemia results in the activation of three isoforms of NOS (nitric oxide synthase) that contribute to the development of and recovery from stroke pathology. This review discusses, in particular, the role of the transcriptionally activated NOS-2 (inducible NOS) isoform and summarizes the outcomes of experimental stroke studies with regard to the therapeutic utility of nitric oxide donors and NOS inhibitors.

A Unique Role of NO in the Control of Blood Flow

Physiology ◽  
1999 ◽  
Vol 14 (2) ◽  
pp. 74-80 ◽  
Author(s):  
Ulrich Pohl ◽  
Cor de Wit
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Vascular Conductance ◽  
Unique Role ◽  
Nos Inhibitors ◽  
Oxide Synthase

Nitric oxide synthase (NOS) inhibitors induce significant vasoconstriction, suggesting an indispensable role of NO as a local vasodilator. This is due mainly to its effects on large arterioles that significantly control arterial conductance while scarcely being regulated by metabolites. NO’s role in adapting vascular conductance to flow is pronounced during (re)active hyperemia and autoregulation.

scholarly journals Experimental Model of Zymosan-Induced Arthritis in the Rat Temporomandibular Joint: Role of Nitric Oxide and Neutrophils

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Hellíada Vasconcelos Chaves ◽  
Ronaldo de Albuquerque Ribeiro ◽  
André Mattos Brito de Souza ◽  
Antonio Alfredo Rodrigues e Silva ◽  
Antoniella Souza Gomes ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Temporomandibular Joint ◽  
Myeloperoxidase Activity ◽  
Plasma Extravasation ◽  
Neutrophil Accumulation ◽  
Histological Changes ◽  
Leucocyte Migration ◽  
Nos Inhibitors ◽  
Oxide Synthase

Aims. To establish a new model of zymosan-induced temporomandibular joint (TMJ) arthritis in the rat and to investigate the role of nitric oxide.Methods. Inflammation was induced by an intra-articular injection of zymosan into the left TMJ. Mechanical hypernociception, cell influx, vascular permeability, myeloperoxidase activity, nitrite levels, and histological changes were measured in TMJ lavages or tissues at selected time points. These parameters were also evaluated after treatment with the nitric oxide synthase (NOS) inhibitors L-NAME or 1400 W.Results. Zymosan-induced TMJ arthritis caused a time-dependent leucocyte migration, plasma extravasation, mechanical hypernociception, and neutrophil accumulation between 4 and 24 h. TMJ immunohistochemical analyses showed increased inducible NOS expression. Treatment with L-NAME or 1400 W inhibited these parameters.Conclusion. Zymosan-induced TMJ arthritis is a reproducible model that may be used to assess both the mechanisms underlying TMJ inflammation and the potential tools for therapies. Nitric oxide may participate in the inflammatory temporomandibular dysfunction mechanisms.

scholarly journals Human Nitric Oxide Synthase—Its Functions, Polymorphisms, and Inhibitors in the Context of Inflammation, Diabetes and Cardiovascular Diseases

2020 ◽  
Vol 22 (1) ◽  
pp. 56
Author(s):  
Magdalena Król ◽  
Marta Kepinska
Keyword(s):  
Nitric Oxide ◽  
Free Radicals ◽  
Nitric Oxide Synthase ◽  
Cell Damage ◽  
Intercellular Signaling ◽  
Nos Inhibitors ◽  
Genes Encoding ◽  
Oxide Synthase ◽  
Nos Isoforms

In various diseases, there is an increased production of the free radicals needed to carry out certain physiological processes but their excessive amounts can cause oxidative stress and cell damage. Enzymes play a major role in the transformations associated with free radicals. One of them is nitric oxide synthase (NOS), which catalyzes the formation of nitric oxide (NO). This enzyme exists in three forms (NOS1, NOS2, NOS3), each encoded by a different gene. The following work presents the most important information on the NOS isoforms and their role in the human body, including NO synthesis in various tissues and cells, intercellular signaling and activities supporting the immune system and regulating blood vessel functions. The role of NOS in pathological conditions such as obesity, diabetes and heart disease is considered. Attention is also paid to the influence of the polymorphisms of these genes, encoding particular isoforms, on the development of these pathologies and the role of NOS inhibitors in the treatment of patients.

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