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    ANGIOTENSIN (5-8) MODULATES NOCICEPTION AT the RAT PERIAQUEDUCTAL GRAY VIA the NO-sGC PATHWAY and AN ENDOGENOUS OPIOID
    (Elsevier B.V., 2013-02-12) Guethe, L. M.; Pelegrini-da-Silva, A.; Borelli, K. G.; Juliano, M. A. [UNIFESP]; Pelosi, G. G.; Pesquero, J. B. [UNIFESP]; Silva, C. L. M.; Correa, F. M. A.; Murad, F.; Prado, W. A.; Martins, A. R.; Universidade de São Paulo (USP); Univ Fed Triangulo Mineiro; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do Rio de Janeiro (UFRJ); George Washington Univ; Universidade Estadual de Londrina (UEL)
    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.