title: Ang-(1-7) activates the NO/cGMP and ATP-sensitive K+ channels pathway to induce peripheral antinociception in rats.
abstract: 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.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Costa
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Giovane
authors.initials: G
authors.lastname: Galdino
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Romero
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Grazielle
authors.initials: G
authors.lastname: Silva
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Steyner
authors.initials: S
authors.lastname: Cortes
authors.affiliation: Department of Physiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Robson
authors.initials: R
authors.lastname: Santos
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. Electronic address: dimitri@icb.ufmg.br.
authors.forename: Igor
authors.initials: I
authors.lastname: Duarte
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D054086:KATP Channels; D010446:Peptide Fragments; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D000803:Angiotensin I; D001120:Arginine; D006152:Cyclic GMP; C118790:angiotensin I (1-7); D015232:Dinoprostone
keywords: Angiotensin-(1–7); Antinociception; Nitric oxide; Pain