scholarly journals Effects of various nitric oxide synthase inhibitors on quinolinic acid-induced neuronal injury in rats

2004 ◽  
Vol 23 (1) ◽  
pp. 11-18
Author(s):  
Ivana Vasiljevic ◽  
Marina Jovanovic ◽  
Miodrag Colic ◽  
Rosa Mihajlovic ◽  
Mirjana Djukic ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Quinolinic Acid ◽  
Neuronal Injury ◽  
Rat Striatum ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitric Oxide Synthase Inhibitors ◽  
Synthase Inhibitor ◽  
Oxide Synthase

The aetiology of neuronal death in neurodegenerative diseases, including Huntington-s disease, is still unknown. There could be a complex interplay among altered energy metabolism, excitotoxicity and oxidative stress. Our aim was to examine the effects of intrastriatal injection of a selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, and a non-specific potent nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester, in order to study the possible involvement of glutathione, an important antioxidant, in quinolinic acid-induced striatal toxicity in the rat. Unilateral administration of quinolinic acid to rat striatum in a single dose of 150 nmol/L was used as a model of Huntington-s disease. The other group of animals were pretreated with 7- nitroindazole and Nw-nitro-L-arginine methyl ester, respectively. Control groups were treated with saline solution and olive oil, respectively. Content of total glutathione, was increased in the ipsi- and contralateral striatum, forebrain cortex, basal forebrain and hippocampus in the groups treated with nitric oxid synthase inhibitors and quinolinic acid compared to the quinolinic acid-treated animals. These results support the hypothesis that oxygen free radicals contribute to excitotoxic neuronal injury, and also that nitric oxide synthase inhibitors could be potential neuroprotective agents in Huntington-s disease.

scholarly journals Nitric oxide synthase inhibitors prevents quinolinic acid-induced neurotoxicity: the role of nitric oxide and glucose-6-phosphate dehydrogenase in cell death

2002 ◽  
Vol 21 (3) ◽  
pp. 269-274
Author(s):  
Ivana Maksimovic ◽  
Marina Jovanovic ◽  
Miodrag Colic ◽  
Dejan Micic ◽  
Rosa Mihajlovic ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Quinolinic Acid ◽  
Neuronal Damage ◽  
Nitrite Accumulation ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitric Oxide Synthase Inhibitors ◽  
Oxide Synthase ◽  
Glucose 6 Phosphate Dehydrogenase

In the present study we employed Nw-nitro-L-arginine methyl ester, non-specific potent nitric oxide synthase inhibitor and a selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole, reportedly to investigate the possible involvement of nitric oxide in quinolinic acid-induced striatal toxicity in the rat. Quinolinic acid was administered unilaterally into striatum of adult Wistar rats in the single dose of 150 nmol/L. The other two group of animals were pretreated with Nw-nitro-L-arginine methyl ester and 7-nitroindazole respectively. Control groups of animals were treated with 0,154 mmol/L saline solution likewise. Nitrite levels was decreased in the ipsi- and contralateral striatum and forebrain cortex in the group treated with nitric oxide synthase inhibitors and neurotoxin compared to quinolinic acid-treated animals. In the same structures, activity of glucose-6-phosphate dehydrogenase was also decreased, compared to quinolinic acid-treated animals. These results indicate that application of the nitric oxide synthase inhibitors, supressed nitrite accumulation and glucose-6-phosphate dehydrogenase activity and attenuated quinolinic acid-induced neuronal damage in the striatum and forebrain cortex.

The Nitric Oxide Synthase Inhibitor NG-nitro-L-Arginine Methyl Ester Potentiates Insulin Secretion Stimulated by Glucose and L-Arginine Independently of its Action on ATP-Sensitive K+ Channels

1998 ◽  
Vol 18 (1) ◽  
pp. 19-28 ◽  
Author(s):  
Albert Salehi ◽  
Fariborz Parandeh ◽  
Ingmar Lundquist
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Insulin Release ◽  
Glucagon Secretion ◽  
Nitric Oxide Synthase Inhibitor ◽  
Insulin And Glucagon Secretion ◽  
Synthase Inhibitor ◽  
Oxide Synthase

The nature of the action of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on hormone release from isolated islets was investigated. We found that glucose-induced insulin release was potentiated by L-NAME in the absence or presence of diazoxide, a potent K+ATP channel opener, as well as in the presence of diazoxide plus a depolarizing concentration of K+. At a low, physiological glucose concentration L-NAME did not influence insulin secretion induced by K+ but inhibited glucagon secretion. L-arginine-induced insulin release was potentiated by L-NAME. This potentiation was observed also in the presence of K+ plus diazoxide. Further, glucagon release induced by L-arginine as well as by L-arginine plus K+ and diazoxide was suppressed by L-NAME. The results strongly suggest that the L-NAME-induced potentiation of insulin secretion in response to glucose or L-arginine as well as the inhibitory effects on glucagon secretion are largely mediated by L-NAME directly suppressing islet NOS activity. Hence NO apparently affects insulin and glucagon secretion independently of membrane depolarization events.

Endothelial-mediated dilations of rat middle cerebral arteries by ATP and ADP

1997 ◽  
Vol 273 (3) ◽  
pp. H1472-H1477 ◽  
Author(s):  
J. You ◽  
T. D. Johnson ◽  
W. F. Childres ◽  
R. M. Bryan
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Cerebral Arteries ◽  
Nitric Oxide Synthase Inhibitor ◽  
Middle Cerebral Arteries ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Maximum Removal

The hypothesis that ATP and ADP produce dilations of rat middle cerebral arteries (MCAs) by different mechanisms was tested. Vessel diameters were measured from pressurized, perfused MCAs after application of different agonists. The luminal administration of ATP and ADP elicited concentration-dependent dilations (35% maximum). Removal of endothelium abolished the dilation to intraluminal ATP and attenuated the dilation to intraluminal ADP. The dilations to ATP were abolished with N omega-nitro-L-arginine methyl ester (L-NAME; 10 microM), a nitric oxide synthase inhibitor, at ATP concentrations of 1 microM and below. However, at concentrations of 10 microM ATP and above, L-NAME had no effect on the response. The dilations to ADP were attenuated by L-NAME to the same degree as removal of endothelium. The mechanism for dilation by ATP was identical to that of UTP, a selective P2u purinoceptor agonist. The mechanism of dilation by ADP was similar to that of 2-methylthioadenosine 5'-triphosphate, a selective P2y purinoceptor agonist. We conclude that ATP and ADP elicit dilations of rat MCA by different mechanisms. ATP and ADP likely stimulate P2u and P2y purinoceptors, respectively.

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