5 research outputs found

    Angiotensin (5-8) modulates nociception at the rat periaqueductal gray via the NO-sGC pathway and an endogenous opioid

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    Angiotensins (Angs) modulate blood pressure, hydro-electrolyte composition, and antinociception. Although Ang (5-8) has generally been considered to be inactive, we show here that Ang (5-8) was the smallest Ang to elicit dose-dependent responses and receptor-mediated antinociception in the rat ventrolateral periaqueductal gray matter (vlPAG). Ang (5-8) antinociception seems to be selective, because it did not alter blood pressure or act on vascular or intestinal smooth muscle cells. the non-selective Ang-receptor (Ang-R) antagonist saralasin blocked Ang (5-8) antinociception, but selective antagonists of Ang-R types I, II, IV, and Mas did not, suggesting that Ang (5-8) may act via an unknown receptor. Endopeptidase EP 24.11 and amastatin-sensitive aminopeptidase from the vlPAG catalyzed the synthesis (from Ang II or Ang III) and inactivation of Ang (5-8), respectively. Selective inhibitors of neuronal-nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and a nonselective opioid receptor (opioid-R) inhibitor blocked Ang (5-8)-induced antinociception. in conclusion, Ang (5-8) is a new member of the Ang family that selectively and strongly modulates antinociception via NO-sGC and endogenous opioid in the vlPAG. (c) 2012 IBRO. Published by Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FFCLRP Univ São Paulo, Dept Psychol, BR-14049901 Ribeirao Preto, BrazilUniv São Paulo, Inst Neurosci & Behav INeC, BR-14049901 Ribeirao Preto, SP, BrazilUniv São Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP, BrazilUniv Fed Triangulo Mineiro, Inst Biol Sci, BR-38025015 Uberaba, MG, BrazilEscola Paulista Med UNIFESP, Dept Biophys, BR-04044020 São Paulo, BrazilUniv Fed Rio de Janeiro, ICB, Cellular & Mol Pharmacol Res Program, BR-21941599 Rio de Janeiro, RJ, BrazilGeorge Washington Univ, Dept Biochem & Mol Biol, Washington, DC 20037 USAUniv Estadual Londrina, Dept Physiol Sci, Ctr Biol Sci, BR-86055900 Londrina, PR, BrazilEscola Paulista Med UNIFESP, Dept Biophys, BR-04044020 São Paulo, BrazilCNPq: 306008/2009-2CNPq: 561151/2010-5CNPq: 472474/2010-3CNPq: 476394/2012-0CNPq: 159841/2010-0FAPESP: 2008/06676-8Web of Scienc
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