Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/326431
Type: Artigo
Title: Pharmacological Analysis Of Hemodynamic Responses To Lachesis Muta (south American Bushmaster) Snake Venom In Anesthetized Rats
Author: Dias
Lourdes; Rodrigues
Mariana A. P.; Inoue
Bruna R.; Rodrigues
Renata L.; Renno
Andre L.; de Souza
Valeria B.; Torres-Huaco
Frank D.; Sousa
Norma C.; Stroka
Alessandra; Melgarejo
Anibal R.; Hyslop
Stephen
Abstract: In this work, we examined some mechanisms involved in the hypotension caused by Lachesis muta (South American bushmaster) venom in anesthetized rats. Venom (1.5 mg/kg, i.v.) caused immediate hypotension that was maximal after 5 min and gradually returned to baseline over 60 min. Pretreatment of rats with the non-selective nitric oxide synthase (NOS) inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) did not attenuate the early phase of venom-induced hypotension, but abolished the recovery phase and resulted in rapid death; a similar effect was observed with the soluble guanylate cyclase (sGC) inhibitor ODQ. In contrast, the hemodynamic responses to venom were not attenuated by the nonselective NOS inhibitor N-G-monomethyl-L-arginine, the inducible NOS inhibitor aminoguanidine, the phosphodiesterase 5 inhibitor sildenafil, the adenylate cyclase (AC) inhibitor SQ-22.536, the nonselective muscarinic receptor antagonist atropine, the bradykinin B2 receptor antagonist HOE-140 and the non-selective cyclooxygenase inhibitor indomethacin. Preincubation of venom with the PLA(2) inhibitor pBPB had no effect on the immediate hypotension but tended to improve the recovery phase. Neither AEBSF (a serine proteinase inhibitor) nor EDTA (a metalloproteinase inhibitor) prevented the venom-induced hypotension, but AEBSF and not EDTA protected against the lethality of a high dose (3.0 mg/kg, i.v.). There were no marked changes in the ECG parameters with the various treatments, except with L-NAME and ODQ that increased the RR interval. Pulmonary thrombus formation was markedly enhanced by L-NAME and ODQ, and to a lesser extent by pBPB, especially in small vessels, whereas AEBSF and EDTA inhibited thrombus formation. Venom relaxed phenylephrine-precontracted thoracic aorta and pulmonary artery in vitro, with the latter being more sensitive. The relaxation was endothelium-dependent and was inhibited by ODQ but not by H-89, a protein kinase A (PKA) inhibitor. Together, these findings indicate involvement of the NO/sGC/cGMP, but not the AC/cAMP/PKA signaling pathway, in the hemodynamic responses to L muta venom in rats. Muscarinic mechanisms, kinins and arachidonic acid metabolites are apparently not involved. (C) 2016 Elsevier Ltd. All rights reserved.
Subject: Cholinergic Neurotransmission
Hypotension
Kinin
Lachesis Muta Venom
Nitric Oxide
Pulmonary Thrombosis
Editor: Pergamon-Elsevier Science LTD
Oxford
Rights: fechado
Identifier DOI: 10.1016/j.toxicon.2016.10.002
Address: http://www-sciencedirect-com.ez88.periodicos.capes.gov.br/science/article/pii/S0041010116302951
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

Files in This Item:
File SizeFormat 
000389117100003.pdf3.98 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.