Blockade of the renin-angiotensin system suppresses hydroxyl radical production in the rat striatum during carbon monoxide poisoning.
Sci Rep
; 10(1): 2602, 2020 02 13.
Article
in En
| MEDLINE
| ID: mdl-32054947
ABSTRACT
Oxidative stress has been suggested to play a role in brain damage during carbon monoxide (CO) poisoning. Severe poisoning induced by CO at 3000 ppm, but not 1000 ppm, enhances hydroxyl radical (ËOH) production in the rat striatum, which might be mediated by NADPH oxidase (NOX) activation associated with Ras-related C3 botulinum toxin substrate (Rac) via cAMP signaling pathway activation. CO-induced ËOH production was suppressed by antagonists of angiotensin II (AngII) type 1 receptor (AT1R) and type 2 receptor (AT2R) but not an antagonist of the Mas receptor. Suppression by an AT1R antagonist was unrelated to peroxisome proliferator-activated receptor γ. Angiotensin-converting enzyme inhibitors also suppressed CO-induced ËOH production. Intrastriatal AngII at high concentrations enhanced ËOH production. However, the enhancement of ËOH production was resistant to inhibitors selective for NOX and Rac and to AT1R and AT2R antagonists. This indicates a different mechanism for ËOH production induced by AngII than for that induced by CO poisoning. AT1R and AT2R antagonists had no significant effects on CO-induced cAMP production or ËOH production induced by forskolin, which stimulates cAMP production. These findings suggest that the renin-angiotensin system might be involved in CO-induced ËOH production in a manner independent of cAMP signaling pathways.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Renin-Angiotensin System
/
Carbon Monoxide Poisoning
/
Hydroxyl Radical
/
Corpus Striatum
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Angiotensin II Type 1 Receptor Blockers
/
Angiotensin II Type 2 Receptor Blockers
Limits:
Animals
Language:
En
Journal:
Sci Rep
Year:
2020
Document type:
Article
Affiliation country:
Japan