Nitric oxide (NO) serves as a retrograde messenger to activate neuronal NO synthase in the spinal cord via NMDA receptors

Nitric Oxide ◽  
2007 ◽  
Vol 17 (1) ◽  
pp. 18-24 ◽  
Author(s):  
Li Xu ◽  
Tamaki Mabuchi ◽  
Tayo Katano ◽  
Shinji Matsumura ◽  
Emiko Okuda-Ashitaka ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Nmda Receptors ◽  
No Synthase ◽  
Neuronal No Synthase ◽  
Retrograde Messenger

Activation of Spinal N-methyl-D-aspartate Receptors Stimulates a Nitric Oxide/Cyclic Guanosine 3′,5′-monophosphate/Glutamate Release Cascade in Nociceptive Signaling 

1999 ◽  
Vol 91 (5) ◽  
pp. 1415-1415 ◽  
Author(s):  
Tomoyuki Kawamata ◽  
Keiichi Omote
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Nmda Receptors ◽  
Soluble Guanylate Cyclase ◽  
Glutamate Release ◽  
No Synthase ◽  
Nociceptive Transmission ◽  
Glutamate Concentration ◽  
Cgmp Pathway ◽  
Synthase Inhibitor

Background Increasing evidence has suggested the possibility that the activation of N-methyl-D-aspartate (NMDA) receptors modulates spinal nociceptive transmission via a nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) pathway. However, the existence and the role of an NO/cGMP pathway in the modulation of spinal nociceptive transmission has been unclear. The authors hypothesized that the activation of NMDA receptors stimulates an NO/cGMP pathway, and this pathway evokes glutamate release within the spinal cord, modulating spinal nociceptive transmission. Methods The authors have examined the effects of an NO synthase inhibitor and a soluble guanylate cyclase inhibitor on the concentrations of NO metabolites (NO2-/NO3-) and glutamate in the cerebrospinal fluid after intrathecal perfusion of NMDA, concomitantly observing pain-related behavior (scratching, biting, and vocalization) in unanesthetized, free-moving rats using an intrathecal microdialysis method. The contents of cGMP in the dorsal horn were also measured using enzyme immunoassay method. Results Intrathecal perfusion of NMDA produced pain-related behavior and increased glutamate and NO2-/NO3-concentrations in a dose-dependent manner. A competitive NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid, completely blocked the NMDA-induced responses. An NO synthase inhibitor, N(G)-monomethyl-L-arginine acetate, at a dose that completely blocked the increase in NO2-/NO3-, inhibited both the NMDA-induced pain-related behavior and the increase in glutamate concentration. In addition, a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazole[4,3-a]quinoxaline-1-one, also inhibited significantly NMDA-induced pain-related behavior and the increase in glutamate concentration. NMDA induced an increase in cGMP in the dorsal half of the spinal cord, which was blocked by N(G)-monomethyl-L-arginine acetate. Conclusions The results of this study support the hypothesis that the activation of NMDA receptors modulated pain-related behavior via an NO/cGMP/glutamate release cascade within the spinal cord.

scholarly journals Neuronal Nitric Oxide Synthase and Ischemia-Induced Neurogenesis

2005 ◽  
Vol 25 (4) ◽  
pp. 485-492 ◽  
Author(s):  
Yunjuan Sun ◽  
Kunlin Jin ◽  
Jocelyn T Childs ◽  
Lin Xie ◽  
Xiao Ou Mao ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Focal Cerebral Ischemia ◽  
Selective Inhibition ◽  
No Synthase ◽  
Adult Brain ◽  
Brdu Incorporation ◽  
Neuronal No Synthase ◽  
Synthase Inhibitor

Nitric oxide (NO) influences infarct size after focal cerebral ischemia and also regulates neurogenesis in the adult brain. These observations suggest that therapeutic approaches to stroke that target NO signaling may provide neuroprotection and also enhance brain repair through cell replacement. However, ischemic injury and neurogenesis are both affected differently depending on which isoform of NO synthase is the source of NO. In addition, ischemia itself stimulates neurogenesis, and ischemia-induced neurogenesis may be regulated differently than neurogenesis in nonischemic brain. To determine how neuronal NO synthase affects ischemia-induced neurogenesis, transient focal cerebral ischemia was produced in wild-type mice and in knockout mice lacking neuronal NO synthase, and BrdU incorporation and doublecortin immunoreactivity were measured in the principal neuroproliferative regions of the adult brain. Knockout of neuronal NO synthase reduced infarct size and increased both basal and ischemia-induced neurogenesis, suggesting that NO from this source is an inhibitory regulator of neurogenesis in the ischemic brain. 7-Nitroindazole, an NO synthase inhibitor that preferentially affects the neuronal isoform, also increased neurogenesis in rats when administered by the intracerebroventricular route. Selective inhibition of neuronal NO synthase may have the potential to both reduce infarct size and enhance neurogenesis in stroke.

Resistance of PC12 cells against nitric oxide (NO)-induced toxicity in long-term culture: implication of neuronal NO synthase expression

2001 ◽  
Vol 309 (3) ◽  
pp. 169-172 ◽  
Author(s):  
Kohei Yuyama ◽  
Hideko Yamamoto ◽  
Kazuhiro Nakamura ◽  
Takeshi Kato ◽  
Ichiro Sora ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pc12 Cells ◽  
No Synthase ◽  
Neuronal No Synthase ◽  
Long Term Culture

scholarly journals Nitric Oxide in the Spinal Cord Is Involved in the Hyperalgesia Induced by Tetrahydrobiopterin in Chronic Restraint Stress Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Ying Huang ◽  
Bo Jiao ◽  
Bo Zhu ◽  
Bingrui Xiong ◽  
Pei Lu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Restraint Stress ◽  
Intrathecal Injection ◽  
Thermal Hyperalgesia ◽  
No Synthase ◽  
Stressful Event ◽  
Inos Mrna ◽  
No Production ◽  
Pain Symptoms

It has been well recognized that exposure to chronic stress could increase pain responding and exacerbate pain symptoms, resulting in stress-induced hyperalgesia. However, the mechanisms underlying stress-induced hyperalgesia are not yet fully elucidated. To this end, we observed that restraint as a stressful event exacerbated mechanical and thermal hyperalgesia, accompanied with up-regulation of nitric oxide (NO) (P < 0.001), GTP cyclohydrolase 1 (GCH1) (GCH1 mRNA: P = 0.001; GCH1 protein: P = 0.001), and tetrahydrobiopterin (BH4) concentration (plasma BH4: P < 0.001; spinal BH4: P < 0.001) on Day 7 in restraint stress (RS) rats. Intrathecal injection of Nω-nitro-L-arginine methyl ester (L-NAME), a non-specific NO synthase inhibitor, or N-([3-(aminomethyl)phenyl]methyl) ethanimidamide, a special inhibitor of inducible NO synthase (iNOS), for seven consecutive days attenuated stress-induced hyperalgesia and decreased the production of NO (P < 0.001). Interestingly, 7-nitro indazole, a special inhibitor of neuronal NO synthase, alleviated stress-induced hyperalgesia but did not affect spinal NO synthesis. Furthermore, intrathecal injection of BH4 not only aggravated stress-induced hyperalgesia but also up-regulated the expression of spinal iNOS (iNOS mRNA: P = 0.015; iNOS protein: P < 0.001) and NO production (P < 0.001). These findings suggest that hyperalgesia induced by RS is associated with the modulation of the GCH1–BH4 system and constitutively expressed spinal iNOS. Thus, the GCH1–BH4–iNOS signaling pathway may be a new novel therapeutic target for pain relief in the spinal cord.

scholarly journals Blockade of neuronal nitric oxide synthase alters the baroreflex control of heart rate in the rabbit

1998 ◽  
Vol 274 (1) ◽  
pp. R181-R186 ◽  
Author(s):  
Hiroshi Murakami ◽  
Jun-Li Liu ◽  
Hirohito Yoneyama ◽  
Yasuhiro Nishida ◽  
Kenji Okada ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
No Synthase ◽  
Baroreflex Control ◽  
Neuronal No Synthase ◽  
Significant Difference ◽  
Before And After ◽  
Synthase Inhibitor ◽  
Oxide Synthase

In previous studies we used N G-nitro-l-arginine (l-NNA) to investigate the role of nitric oxide (NO) in baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA).l-NNA increased resting mean arterial pressure (MAP), decreased HR, and did not change or slightly decreased RSNA. These changes complicated the assessment of the central effects of NO on the baroreflex control of HR and RSNA. Therefore, in the present study the effects of the relatively selective neuronal NO synthase inhibitor 7-nitroindazole (7-NI) on the baroreflex control of HR and RSNA were investigated in rabbits. Intraperitoneal injection of 7-NI (50 mg/kg) had no effect on resting HR, MAP, or RSNA. 7-NI significantly reduced the lower plateau of the HR-MAP baroreflex curve from 140 ± 4 to 125 ± 4 and from 177 ± 10 to 120 ± 9 beats/min in conscious and anesthetized preparations, respectively ( P < 0.05). In contrast, there was no significant difference in the RSNA-MAP curves before and after 7-NI administration in conscious or anesthetized preparations. These data suggest that blockade of neuronal NO synthase influences baroreflex control of HR but not of RSNA in rabbits.

scholarly journals Involvement of N-methyl-D-aspartate receptors and nitric oxide in the anticonvulsant effects of dantrolene against pentylenetetrazole-induced seizures in mice

2017 ◽  
Vol 04 (02) ◽  
pp. 112-118
Author(s):  
Akbarzadeh Samad ◽  
Heidary Fatemeh ◽  
Keshavarz Mojtaba
Keyword(s):  
Nitric Oxide ◽  
Nmda Receptors ◽  
Clonic Seizure ◽  
Negative Control ◽  
No Synthase ◽  
Tonic Clonic Seizure ◽  
Control Group ◽  
No Donor ◽  
Clonic Seizures ◽  
Anticonvulsant Effects

Abstract Objective N-methyl-d-aspartate (NMDA) receptors and nitric oxide (NO) have important roles in the pathology and treatment of pentylenetetrazole (PTZ)-induced seizures. We aimed to show the involvement of these two systems in the anticonvulsant effects of dantrolene against PTZ-induced seizures. Methods The male albino Swiss strain of mice (N = 56) randomly allocated to the seven separate groups and treated with dantrolene (40 mg/kg), dantrolene (40 mg/kg) + L-arginine (100 mg/kg, a NO donor), dantrolene (40 mg/kg) + N-Nitroarginine methyl ester (L-NAME) (100 mg/kg, a NO synthase inhibitor), dantrolene (40 mg/kg) + NMDA (50 mg/kg), dantrolene (40 mg/kg) + MK801 (1 mg/kg, a selective NMDA antagonist), Diazepam (5 mg/kg, the positive control) and saline (the negative control). Seizures were induced by intraperitonial injection of PTZ (90 mg/kg). The onsets of clonic and tonic-clonic seizures, as well as the death of animals, were recorded. Results Dantrolene significantly increased the onset of clonic, tonic-clonic seizures and death of animals challenged with PTZ. The onset of tonic-clonic seizure in animals treated with dantrolene alone and dantrolene + L-NAME was higher than the control group. In contrast, the onset of tonic-clonic seizure in the animals treated with dantrolene + L-arginine was significantly lower than the dantrolene-treated group. The onset of clonic and tonic-clonic seizures in animals treated with dantrolene + MK801 were significantly higher than the control and dantrolene + NMDA groups. Conclusion Dantrolene protected animals against PTZ-induced seizures and mortality. The inhibition of NO synthase and NMDA receptors may contribute to the dantrolene anticonvulsant effects on the PTZ-induced seizure.

scholarly journals Suppression of Nitric Oxide (NO)-Dependent Behavior by Double-Stranded RNA-Mediated Silencing of a Neuronal NO Synthase Gene

2002 ◽  
Vol 22 (11) ◽  
pp. RC227-RC227 ◽  
Author(s):  
Sergei A. Korneev ◽  
Ildikó Kemenes ◽  
Volko Straub ◽  
Kevin Staras ◽  
Elena I. Korneeva ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Double Stranded Rna ◽  
Neuronal No Synthase ◽  
Dependent Behavior

scholarly journals Nitric Oxide from Neuronal No-Synthase Increases after Beta-Adrenergic Stimulation but does not Control Mitochondrial Respiration in Cardiac Myocytes

2014 ◽  
Vol 106 (2) ◽  
pp. 184a-185a
Author(s):  
Michael Kohlhaas ◽  
Stefanie Bergem ◽  
Alexander Nickel ◽  
Maxie Meiser ◽  
Barbara Casadei ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiac Myocytes ◽  
Mitochondrial Respiration ◽  
No Synthase ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Neuronal No Synthase

Nasal Nitric Oxide Levels in Cystic Fibrosis Patients Are Associated with a Neuronal NO Synthase (NOS1) Gene Polymorphism

Nitric Oxide ◽  
2002 ◽  
Vol 6 (2) ◽  
pp. 236-241 ◽  
Author(s):  
H. Grasemann ◽  
K. Storm van's Gravesande ◽  
S. Gärtig ◽  
M. Kirsch ◽  
R. Büscher ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cystic Fibrosis ◽  
Gene Polymorphism ◽  
No Synthase ◽  
Neuronal No Synthase ◽  
Nasal Nitric Oxide

The role of nitric oxide in the development of neurogenic pulmonary edema in spinal cord-injured rats: the effect of preventive interventions

2009 ◽  
Vol 297 (4) ◽  
pp. R1111-R1117 ◽  
Author(s):  
Jiří Šedý ◽  
Josef Zicha ◽  
Jaroslav Kuneš ◽  
Aleš Hejčl ◽  
Eva Syková
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Spinal Cord ◽  
Heart Rate ◽  
Pulmonary Edema ◽  
No Synthase ◽  
Neurogenic Pulmonary Edema ◽  
Therapeutic Effects ◽  
Cord Injury

Neurogenic pulmonary edema (NPE) is an acute life-threatening complication following an injury of the spinal cord or brain, which is associated with sympathetic hyperactivity. The role of nitric oxide (NO) in NPE development in rats subjected to balloon compression of the spinal cord has not yet been examined. We, therefore, pretreated Wistar rats with the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) either acutely (just before the injury) or chronically (for 4 wk prior to the injury). Acute (but not chronic) l-NAME administration enhanced NPE severity in rats anesthetized with 1.5% isoflurane, leading to the death of 83% of the animals within 10 min after injury. Pretreatment with either the ganglionic blocker pentolinium (to reduce blood pressure rise) or the muscarinic receptor blocker atropine (to lessen heart rate decrease) prevented or attenuated NPE development in these rats. We did not observe any therapeutic effects of atropine administered 2 min after spinal cord compression. Our data indicate that NPE development is dependent upon a marked decrease of heart rate under the conditions of high blood pressure elicited by the activation of the sympathetic nervous system. These hemodynamic alterations are especially pronounced in rats subjected to acute NO synthase inhibition. In conclusion, nitric oxide has a partial protective effect on NPE development because it attenuates sympathetic vasoconstriction and consequent baroreflex-induced bradycardia following spinal cord injury.

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