Ang-(1-7) activates the NO/cGMP and ATP-sensitive K+ channels pathway to induce peripheral antinociception in rats.
Nitric Oxide
; 37: 11-6, 2014 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-24361899
Angiotensin-(1-7) is a bioactive component of the renin-angiotensin system that is formed endogenously and induces nitric oxide release in several tissues. The L-arginine/NO/cyclic GMP pathway and ATP-sensitive K+ channels have been proposed as the mechanism of action for the peripheral antinociception of several groups of drug and endogenous substances, including opioids, non-steroidal analgesics, acetylcholine and others. The aim of the present study was to investigate the involvement of the L-arginine/NO/cGMP and KATP+ pathway on antinociception induced by angiotensin-(1-7). Paw pressure in rats was used to induce hyperalgesia via an intraplantar injection of prostaglandin E2 (2 µg/paw). Ang-(1-7) (2, 3 and 4 µg/paw) elicited a local peripheral antinociceptive effect that was antagonized by the nonselective NO synthase (NOS) inhibitor L-NOarg and the selective neuronal NOS (nNOS) inhibitor L-NPA. The selective inhibition of endothelial (eNOS) and inducible (iNOS) NOS by L-NIO and L-NIL, respectively, was ineffective at blocking the effects of a local Ang-(1-7) injection. In addition, the level of nitrite in the homogenized paw tissue, as determined by a colorimetric assay, indicated that exogenous Ang-(1-7) is able to induce NO release. The soluble guanylyl cyclase inhibitor ODQ and the specific blocker of ATP-sensitive K+ channels glibenclamide (40, 80 and 160 µg/paw) antagonized the Ang-(1-7) response. The results provide evidence that Ang-(1-7) most likely induces peripheral antinociceptive effects via the L-arginine/NO/cGMP pathway and KATP+ pathway activation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dor
/
Fragmentos de Peptídeos
/
Angiotensina I
/
Trifosfato de Adenosina
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GMP Cíclico
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Canais KATP
/
Analgésicos
/
Óxido Nítrico
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nitric Oxide
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos