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.

Hepatic portal venous delivery of a nitric oxide synthase inhibitor enhances net hepatic glucose uptake

2008 ◽  
Vol 294 (4) ◽  
pp. E768-E777 ◽  
Author(s):  
Mary Courtney Moore ◽  
Catherine A. DiCostanzo ◽  
Marta S. Smith ◽  
Ben Farmer ◽  
Tiffany D. Rodewald ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
No Donor ◽  
Nitric Oxide Synthase Inhibitor ◽  
Significant Difference ◽  
Nos Inhibitors ◽  
Hepatic Glucose ◽  
Hepatic Portal ◽  
Oxide Synthase ◽  
Arterial Glucose

Hepatic portal venous infusion of nitric oxide synthase (NOS) inhibitors causes muscle insulin resistance, but the effects on hepatic glucose disposition are unknown. Conscious dogs underwent a hyperinsulinemic (4-fold basal) hyperglycemic (hepatic glucose load 2-fold basal) clamp, with assessment of liver metabolism by arteriovenous difference methods. After 90 min (P1), dogs were divided into two groups: control (receiving intraportal saline infusion; n = 8) and LN [receiving NG-nitro-l-arginine methyl ester (l-NAME), a nonspecific NOS inhibitor; n = 11] intraportally at 0.3 mg·kg−1·min−1 for 90 min (P2). During the final 60 min of study (P3), l-NAME was discontinued, and five LN dogs received the NO donor SIN-1 intraportally at 6 μg·kg−1·min−1 while six received saline (LN/SIN-1 and LN/SAL, respectively). Net hepatic fractional glucose extraction (NHFE) in control dogs was 0.034 ± 0.016, 0.039 ± 0.015, and 0.056 ± 0.019 during P1, P2, and P3, respectively. NHFE in LN was 0.045 ± 0.009 and 0.111 ± 0.007 during P1 and P2, respectively ( P < 0.05 vs. control during P2), and 0.087 ± 0.009 and 0.122 ± 0.016 ( P < 0.05) during P3 in LN/SIN-1 and LN/SAL, respectively. During P2, arterial glucose was 204 ± 5 vs. 138 ± 11 mg/dl ( P < 0.05) in LN vs. control to compensate for l-NAME's effect on blood flow. Therefore, another group (LNlow; n = 4) was studied in the same manner as LN/SAL, except that arterial glucose was clamped at the same concentrations as in control. NHFE in LNlow was 0.052 ± 0.008, 0.093 ± 0.023, and 0.122 ± 0.021 during P1, P2, and P3, respectively ( P < 0.05 vs. control during P2 and P3), with no significant difference in glucose infusion rates. Thus, NOS inhibition enhanced NHFE, an effect partially reversed by SIN-1.

Glomerular and tubular interactions between renal adrenergic activity and nitric oxide

1995 ◽  
Vol 268 (6) ◽  
pp. F1004-F1008 ◽  
Author(s):  
F. B. Gabbai ◽  
S. C. Thomson ◽  
O. Peterson ◽  
L. Wead ◽  
K. Malvey ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Glomerular Filtration ◽  
Renal Nerves ◽  
Ang Ii ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adrenergic Activity ◽  
Single Nephron ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Endothelium-dependent nitric oxide (EDNO) exerts control over the processes of glomerular filtration and tubular reabsorption. The importance of the renal nerves to the tonic influence of EDNO in the glomerular microcirculation and proximal tubule was tested by renal micropuncture in euvolemic adult male Munich-Wistar rats. The physical determinants of glomerular filtration and proximal reabsorption were assessed before and during administration of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in control animals and in animals 5–9 days after either ipsilateral surgical renal denervation (DNX) or after either sham surgery (SHX). L-NMMA caused single-nephron glomerular filtration rate to decline in control and SHX animals but not in DNX rats. L-NMMA caused a reduction in proximal reabsorption in control and SHX rats, which was prevented by prior DNX. DNX did not alter urinary guanosine 3',5'-cyclic monophosphate excretion, and, although DNX upregulates glomerular angiotensin II (ANG II) receptors, prior DNX did not alter intrarenal ANG II content as evaluated by radioimmunoassay. Some component of renal adrenergic activity is required for the full expression of the glomerular and tubular effects of blockade of nitric oxide synthase.

Effects of Early Neuronal and Delayed Inducible Nitric Oxide Synthase Blockade on Cardiovascular, Renal, and Hepatic Function in Ovine Sepsis

2010 ◽  
Vol 113 (6) ◽  
pp. 1376-1384 ◽  
Author(s):  
Matthias Lange ◽  
Atsumori Hamahata ◽  
Daniel L. Traber ◽  
Yoshimitsu Nakano ◽  
Aimalohi Esechie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Plasma Nitrite ◽  
Oxide Synthase ◽  
Organ Dysfunctions ◽  
Inducible Nitric Oxide

Background Recent evidence suggests that nitric oxide produced via the neuronal nitric oxide synthase is involved mainly in the early response to sepsis, whereas nitric oxide derived from the inducible nitric oxide synthase is responsible during the later phase. We hypothesized that early neuronal and delayed inducible nitric oxide synthase blockade attenuates multiple organ dysfunctions during sepsis. Methods Sheep were randomly allocated to sham-injured, nontreated animals (n = 6); injured (48 breaths of cotton smoke and instillation of Pseudomonas aeruginosa into the lungs), nontreated animals (n = 7); and injured animals treated with a neuronal nitric oxide synthase inhibitor from 1 to 12 h and an inducible nitric oxide synthase inhibitor from 12 to 24 h postinjury (n = 6). Results The injury induced arterial hypotension, vascular leakage, myocardial depression, and signs of renal and hepatic dysfunctions. The treatment significantly attenuated, but did not fully prevent, the decreases in mean arterial pressure and left ventricular stroke work index. Although the elevation of creatinine levels was partially prevented, the decreases in urine output and creatinine clearance were not affected. The injury-related increases in bilirubin levels, international normalized ratio, and lipid peroxidation in liver tissue were significantly attenuated. Although plasma nitrite/nitrate levels were significantly increased versus baseline from 12-24 h in controls, plasma nitrite/nitrate levels were not increased in treated animals. Conclusions The combination treatment shows potential benefit on sepsis-related arterial hypotension and surrogate parameters of organ dysfunctions in sheep. It may be crucial to identify the time course of expression and activation of different nitric oxide synthase isoforms in future investigations.

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