Advanced

Nitric oxide synthase inhibitors influence dynorphin A (1-17) immunoreactivity in the rat brain following hyperthermia

Sharma, HS and Alm, Per LU (2002) In Amino Acids 23(1-3). p.247-259
Abstract
The possibility that nitric oxide synthase (NOS) inhibitors influence dynorphin immunoreactivity following hyperthermia was examined in a rat model using a pharmacological approach. Previous reports from our laboratory show that hyperthermia induces an upregulation of NOS in several brain regions that seems to be instrumental in causing cell injury. Recent reports suggest that nitric oxide (NO) can influence dynorphin neurotransmission in the normal brain as well as in several pathological states. Since dynorphin is neurotoxic in different animal models of brain or spinal cord injury, it may be that the peptide will contribute to the cell injury in hyperthermia. The present investigation was carried out to determine whether hyperthermia... (More)
The possibility that nitric oxide synthase (NOS) inhibitors influence dynorphin immunoreactivity following hyperthermia was examined in a rat model using a pharmacological approach. Previous reports from our laboratory show that hyperthermia induces an upregulation of NOS in several brain regions that seems to be instrumental in causing cell injury. Recent reports suggest that nitric oxide (NO) can influence dynorphin neurotransmission in the normal brain as well as in several pathological states. Since dynorphin is neurotoxic in different animal models of brain or spinal cord injury, it may be that the peptide will contribute to the cell injury in hyperthermia. The present investigation was carried out to determine whether hyperthermia can influence dynorphin immunoreactivity in the brain, and if so, whether inhibition of NOS will influence the peptide distribution in the brain following heat stress. Rats subjected to hyperthermia at 38degreesC for 4 h in a biological oxygen demand incubator (BOD) resulted in a marked upregulation of dynorphin immunoreactivity in several brain regions e.g., cerebral cortex, hippocampus, cerebellum and brain stem. Pretreatment of rats with two potent NOS inhibitors, L-NAME (30 mg/kg/day, i.p. for 7 days) or L-NMMA (35 mg/kg/day, i.p. for 7 days) significantly attenuated the dynorphin immunoreactivity in the brain. These drugs were also able to reduce hyperthermia induced blood-brain barrier (BBB) permeability, brain edema formation and cell injury. Taken together, our results suggest that (i) hyperthermia has the capacity to upregulate dynorphin immunoreactivity in the brain, (ii) inhibition of NOS considerably attenuates the dynorphin immunoreaction following heat stress and (iii) upregulation of dynorphin is somehow contributing to hyperthermia induced brain damage, not reported earlier. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
brain edema, nitric oxide synthase, L-NMMA, L-NAME, ultrastructure, nitric oxide, immunoreactivity, brain injury, dynorphin, hyperthermia, [131]iodine, Evans blue
in
Amino Acids
volume
23
issue
1-3
pages
247 - 259
publisher
Springer
external identifiers
  • wos:000178412200036
  • pmid:12373545
  • scopus:0036392023
ISSN
0939-4451
DOI
10.1007/s00726-001-0136-0
language
English
LU publication?
yes
id
cc410794-0720-4e1a-a26f-cf9c2a556577 (old id 326242)
date added to LUP
2007-11-13 14:48:13
date last changed
2017-01-01 04:55:22
@article{cc410794-0720-4e1a-a26f-cf9c2a556577,
  abstract     = {The possibility that nitric oxide synthase (NOS) inhibitors influence dynorphin immunoreactivity following hyperthermia was examined in a rat model using a pharmacological approach. Previous reports from our laboratory show that hyperthermia induces an upregulation of NOS in several brain regions that seems to be instrumental in causing cell injury. Recent reports suggest that nitric oxide (NO) can influence dynorphin neurotransmission in the normal brain as well as in several pathological states. Since dynorphin is neurotoxic in different animal models of brain or spinal cord injury, it may be that the peptide will contribute to the cell injury in hyperthermia. The present investigation was carried out to determine whether hyperthermia can influence dynorphin immunoreactivity in the brain, and if so, whether inhibition of NOS will influence the peptide distribution in the brain following heat stress. Rats subjected to hyperthermia at 38degreesC for 4 h in a biological oxygen demand incubator (BOD) resulted in a marked upregulation of dynorphin immunoreactivity in several brain regions e.g., cerebral cortex, hippocampus, cerebellum and brain stem. Pretreatment of rats with two potent NOS inhibitors, L-NAME (30 mg/kg/day, i.p. for 7 days) or L-NMMA (35 mg/kg/day, i.p. for 7 days) significantly attenuated the dynorphin immunoreactivity in the brain. These drugs were also able to reduce hyperthermia induced blood-brain barrier (BBB) permeability, brain edema formation and cell injury. Taken together, our results suggest that (i) hyperthermia has the capacity to upregulate dynorphin immunoreactivity in the brain, (ii) inhibition of NOS considerably attenuates the dynorphin immunoreaction following heat stress and (iii) upregulation of dynorphin is somehow contributing to hyperthermia induced brain damage, not reported earlier.},
  author       = {Sharma, HS and Alm, Per},
  issn         = {0939-4451},
  keyword      = {brain edema,nitric oxide synthase,L-NMMA,L-NAME,ultrastructure,nitric oxide,immunoreactivity,brain injury,dynorphin,hyperthermia,[131]iodine,Evans blue},
  language     = {eng},
  number       = {1-3},
  pages        = {247--259},
  publisher    = {Springer},
  series       = {Amino Acids},
  title        = {Nitric oxide synthase inhibitors influence dynorphin A (1-17) immunoreactivity in the rat brain following hyperthermia},
  url          = {http://dx.doi.org/10.1007/s00726-001-0136-0},
  volume       = {23},
  year         = {2002},
}