Expression of nitric oxide synthase isoforms in normal ventilatory and limb muscles

1997 ◽  
Vol 83 (2) ◽  
pp. 348-353 ◽  
Author(s):  
Sabah N. A. Hussain ◽  
Qasim El-Dwairi ◽  
Mohammed N. Abdul-Hussain ◽  
Dalia Sakkal
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Fiber Type ◽  
Nos Inhibitors ◽  
Limb Muscles ◽  
Fiber Type Distribution ◽  
Neuronal Nos ◽  
Weak Expression ◽  
Oxide Synthase ◽  
Nos Isoforms

Hussain, Sabah N. A., Qasim El-Dwairi, Mohammed N. Abdul-Hussain, and Dalia Sakkal. Expression of nitric oxide synthase isoforms in normal ventilatory and limb muscles. J. Appl. Physiol. 83(2): 348–353, 1997.—Nitric oxide (NO), an important messenger molecule with widespread actions, is synthesized by NO synthases (NOS). In this study, we investigated the correlation between fiber type and NOS activity among ventilatory and limb muscles of various species. We also assessed the presence of the three NOS isoforms in normal skeletal muscles and how various NOS inhibitors influence muscle NOS activity. NOS activity was detected in various muscles; however, NOS activity in rabbits and rats varied significantly among different muscles. Immunoblotting of muscle samples indicated the presence of both the neuronal NOS and the endothelial NOS isoforms but not the cytokine-inducible NOS isoform. However, these isoforms were expressed to different degrees in various muscles. Although the neuronal NOS isoform was detectable in the canine diaphragm, very weak expression was detected in rabbit, rat, and mouse diaphragms. The endothelial NOS isoform was detected in the rat and mouse diaphragms but not in the canine and rabbit diaphragms. We also found that N G-nitro-l-arginine methyl ester, 7-nitroindazole, and S-methylisothiourea were stronger inhibitors of muscle NOS activity than was aminoguanidine. These results indicate the presence of different degrees of constitutive NOS expression in normal ventilatory and limb muscles of various species. Our data also indicate that muscle NOS activity is not determined by fiber type distribution but by other not yet identified factors. The functional significance of this expression remains to be assessed.

Fire Ant Venom Alkaloid, Isosolenopsin A, a Potent and Selective Inhibitor of Neuronal Nitric Oxide Synthase

2003 ◽  
Vol 22 (2) ◽  
pp. 81-86 ◽  
Author(s):  
G. B. Yi ◽  
D. Mc Clendon ◽  
D. Desaiah ◽  
J. Goddard ◽  
A. Lister ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inhibitory Activity ◽  
Systemic Toxicity ◽  
Fire Ant ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Nos Inhibitors ◽  
Oxide Synthase ◽  
Nos Isoforms

Massive, multiple fire ant, Solenopsis invicta, stings are often treated aggressively, particularly in the elderly, despite limited evidence of systemic toxicity due to the venom. Over 95% of the S. invicta venom is composed of piperidine alkaloid components, whose toxicity, if any, is unknown. To assess a possible pharmacological basis for systemic toxicity, an alkaloid-rich, protein-free methanol extract of the venom from whole ants was assayed for inhibitory activity on the following nitric oxide synthase (NOS) isoforms, rat cerebellar neuronal (n NOS), bovine recombinant endothelial (e NOS), and murine recombinant immunologic (i NOS). Cytosolic NOS activity was determined by measuring the conversion of [3H]arginine to [3H]citrulline in vitro. Rat n NOS activity was inhibited significantly and in a concentration-dependent manner by the alkaloid-rich venom extract. For n NOS, enzyme activity was inhibited by approximately 50% with 0.33 ± 0.06 μgg of this venom extract, and over 95% inhibition of the three isoforms, n NOS, e NOS, and i NOS, was found with doses of 60 μg in 60-μl reaction mixture. These results indicate that the alkaloid components of S. invicta venom can produce potent inhibition of all three major NOS isoforms. Isosolenopsin A ( cis-2-methyl-6-undecylpiperidine), a naturally occurring fire ant piperidine alkaloid, was synthesized and tested for inhibitory activity against the three NOS isoforms. Enzyme activities for n NOS and e NOS were over 95% inhibited with 1000 μM of isosolenopsin A, whereas the activity of i NOS was inhibited by only about 20% at the same concentration. The IC50 for each of three NOS isoforms was approximately 18 ± 3.9 μM for n NOS, 156 ± 10 μM for e NOS, and >1000 μM for i NOS, respectively. Kinetic studies showed isosolenopsin A inhibition to be noncompetitive with L-arginine ( Ki = 19 ± 2 μM). The potency of isosolenopsin A as an inhibitor of n NOS compares favorably with the inhibitory potency of widely used n NOS inhibitors. Inhibition of NOS isoforms by isosolenopsin A and structurally similar compounds may have toxicological significance with respect to adverse reactions to fire ant stings.

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.

Selective neuronal nitric oxide synthase inhibition blocks furosemide-stimulated renin secretion in vivo

1995 ◽  
Vol 269 (1) ◽  
pp. F134-F139 ◽  
Author(s):  
W. H. Beierwaltes
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Macula Densa ◽  
Renin Secretion ◽  
Renal Perfusion Pressure ◽  
Neuronal Nos ◽  
Oxide Synthase

The macula densa is a regulatory site for renin. It contains exclusively the neuronal isoform of nitric oxide synthase (NOS), suggesting NO could stimulate renin secretion through the macula densa pathway. To test whether neuronal NOS mediates renin secretion, renin was stimulated by either the renal baroreceptor or the diuretic furosemide (acting through the macula densa pathway). Renin secretion rate (RSR) was measured in 12 Inactin-anesthetized rats at normal (104 +/- 3 mmHg) and reduced renal perfusion pressure (65 +/- 1 mmHg), before and after selective blockade of the neuronal NOS with 7-nitroindazole (7-NI, 50 mg/kg ip). 7-NI had no effect on basal blood pressure (102 +/- 2 mmHg) or renal blood flow (RBF). Decreasing renal perfusion pressure doubled RSR from 11.8 +/- 3.3 to 22.9 +/- 5.7 ng ANG I.h-1.min-1 (P < 0.01) (ANG I is angiotensin I). Similarly, in 7-NI-treated rats, reduced perfusion doubled RSR from 8.5 +/- 1.8 to 20.5 +/- 6.2 ng ANG I.h-1.min-1 (P < 0.01). Renal hemodynamics and RSR were measured in response to 5 mg/kg iv furosemide in 12 control rats and 11 rats treated with 7-NI. Blocking neuronal NOS did not alter blood pressure (102 +/- 2 mmHg), RBF (5.8 +/- 0.4 ml.min-1.g kidney wt-1), or renal vascular resistance (18.7 +/- 1.4 mmHg.ml-1.min.g kidney wt).(ABSTRACT TRUNCATED AT 250 WORDS)

Selected Contribution: Differential role of nitric oxide synthase isoforms in fever of different etiologies: studies using Nosgene-deficient mice

2003 ◽  
Vol 94 (6) ◽  
pp. 2534-2544 ◽  
Author(s):  
Wieslaw Kozak ◽  
Anna Kozak
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Corn Oil ◽  
Normal Male ◽  
Wild Type ◽  
Oxide Synthase ◽  
And Control ◽  
Nos Isoforms ◽  
Deficient Mice

Male C57BL/6J mice deficient in nitric oxide synthase (NOS) genes (knockout) and control (wild-type) mice were implanted intra-abdominally with battery-operated miniature biotelemeters (model VMFH MiniMitter, Sunriver, OR) to monitor changes in body temperature. Intravenous injection of lipopolysaccharide (LPS; 50 μg/kg) was used to trigger fever in response to systemic inflammation in mice. To induce a febrile response to localized inflammation, the mice were injected subcutaneously with pure turpentine oil (30 μl/animal) into the left hindlimb. Oral administration (gavage) of N G-monomethyl-l-arginine (l-NMMA) for 3 days (80 mg · kg−1 · day−1in corn oil) before injection of pyrogens was used to inhibit all three NOSs ( N G-monomethyl-d-arginine acetate salt and corn oil were used as control). In normal male C57BL/6J mice, l-NMMA inhibited the LPS-induced fever by ∼60%, whereas it augmented fever by ∼65% in mice injected with turpentine. Challenging the respective NOS knockout mice with LPS and with l-NMMA revealed that inducible NOS and neuronal NOS isoforms are responsible for the induction of fever to LPS, whereas endothelial NOS (eNOS) is not involved. In contrast, none of the NOS isoforms appeared to trigger fever to turpentine. Inhibition of eNOS, however, exacerbates fever in mice treated with l-NMMA and turpentine, indicating that eNOS participates in the antipyretic mechanism. These data support the hypothesis that nitric oxide is a regulator of fever. Its action differs, however, depending on the pyrogen used and the NOS isoform.

A radiometric analysis of nitric oxide synthase activity in Hymenolepis diminuta

Parasitology ◽  
2000 ◽  
Vol 120 (1) ◽  
pp. 91-95 ◽  
Author(s):  
N. B. TERENINA ◽  
M. V. ONUFRIEV ◽  
N. V. GULYAEVA ◽  
A. M. LINDHOLM ◽  
M. K. S. GUSTAFSSON
Keyword(s):  
Nitric Oxide ◽  
Free Radical ◽  
Nitric Oxide Synthase ◽  
Nadph Diaphorase ◽  
Hymenolepis Diminuta ◽  
Complete Reduction ◽  
Radiometric Analysis ◽  
Nos Inhibitors ◽  
Oxide Synthase ◽  
Nitric Oxide Synthase Activity

The free radical nitric oxide (NO) is a neuronal messenger which is synthesized from L-arginine and O2 by nitric oxide synthase (NOS). In the synthesis NO and L-citrulline are produced in a stoichiometric 1[ratio ]1 relation. The activity of NOS was analysed in homogenates of the rat tapeworm Hymenolepis diminuta by measuring the formation of L-[3H]citrulline after incubation with L-[3H]arginine. The nature of NOS in H. diminuta was determined by studying the effect of 3 types of NOS inhibitors: (1) L-NAME, (2) EGTA, (3) 7-nitro-indazole. All inhibitors caused a significant but not complete reduction in the formation of L-[3H]citrulline. The results are discussed against the background of nerve cells and fibres positive for NADPH-diaphorase staining in H. diminuta.

Repeated treatment with nitric oxide synthase inhibitor attenuates learned helplessness development in rats and increases hippocampal BDNF expression

2017 ◽  
Vol 30 (3) ◽  
pp. 127-136 ◽  
Author(s):  
Laura Alves Stanquini ◽  
Caroline Biojone ◽  
Francisco Silveira Guimarães ◽  
Sâmia Regiane Joca
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Learned Helplessness ◽  
Positive Control ◽  
Repeated Treatment ◽  
Bdnf Expression ◽  
Nitric Oxide Synthase Inhibitor ◽  
Protein Levels ◽  
Nos Inhibitors ◽  
Oxide Synthase

BackgroundNitric oxide synthase (NOS) inhibitors induce antidepressant-like effects in animal models sensitive to acute drug treatment such as the forced swimming test. However, it is not yet clear if repeated treatment with these drugs is required to induce antidepressant-like effects in preclinical models.ObjectiveThe aim of this study was to test the effect induced by acute or repeated (7 days) treatment with 7-nitroindazole (7-NI), a preferential inhibitor of neuronal NOS, in rats submitted to the learned helplessness (LH) model. In addition, we aimed at investigating if 7-NI treatment would increase brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus, similarly to the effect of prototype antidepressants.MethodsAnimals were submitted to a pre-test (PT) session with inescapable footshocks or habituation (no shocks) to the experimental shuttle box. Six days later they were exposed to a test with escapable footshocks. Independent groups received acute (a single injection after PT or before test) or repeated (once a day for 7 days) treatment with vehicle or 7-NI (30 mg/kg).ResultsRepeated, but not acute, treatment with 7-NI attenuated LH development. The effect was similar to repeated imipramine treatment. Moreover, in an independent experimental group, only repeated treatment with 7-NI and imipramine increased BDNF protein levels in the hippocampus.ConclusionThe results suggest the nitrergic system could be a target for the treatment of depressive-like conditions. They also indicate that, similar to the positive control imipramine, the antidepressant-like effects of NOS inhibition could involve an increase in hippocampal BDNF levels.

scholarly journals 7-Nitro indazole, a neuron-specific nitric oxide synthase inhibitor, produces amnesia in the chick.

1994 ◽  
Vol 1 (4) ◽  
pp. 213-216
Author(s):  
C Hölscher
Keyword(s):  
Nitric Oxide ◽  
Synaptic Plasticity ◽  
Nitric Oxide Synthase ◽  
Blood Vessel ◽  
Passive Avoidance ◽  
Avoidance Task ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nos Inhibitors ◽  
Synthase Inhibitor ◽  
Oxide Synthase

7-Nitro indazole (7-NI), which is selective for the neuronal isoform of nitric oxide synthase (NOS), was tested in a passive avoidance task in the chick. Injection of 50 mg/kg i.p. pretraining had amnesic effects for the task when tested 30 min, 2 or 24 hr after training. Injections post-training had no effect. Because 7-NI does not inhibit the endothelial isoform of NOS, it does not affect blood vessel relaxation, as nonspecific inhibitors do. This effect on blood vessels could explain the amnestic effects produced by nonspecific NOS inhibitors. The results support the theory that NO is a neuronal transmitter that is important in processes of synaptic plasticity and learning.

scholarly journals Nitric oxide synthase in the rat spinotrapezius muscle related to fiber type

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Andrew Thomas Yannaccone ◽  
Mary Shall ◽  
Paul Ratz ◽  
Amy Miner ◽  
Bjorn Song ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Fiber Type ◽  
Oxide Synthase

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.

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