title: The guanylyl cyclase inhibition by MB as vasoplegic circulatory shock therapeutical target.
abstract: There were strong evidences that NO has capital importance in the progressive vasodilatation that associates to the varied circulatory shock forms. The decreased systemic vascular resistance observed in irreversible hemorrhagic (hypovolemic) and septic shock may be due to the excess production of nitric oxide. Other forms of shock associated to anaphylaxis (anaphylactic shock, SIRS) and ischemia reperfusion injury (cardiogenic shock, organ transplants), may involve nitric oxide overproduction. In these situations, the nitric oxide-induced loss of vascular sensitivity to catecholamines and myocardial depression contributes to lethal hypotension. As NO vasodilatation is cyclic GMP-mediated, there were two therapeutical options: a) The unspecific NO synthesis inhibition by L-arginine analogs, iNOS-specific inhibition by corticoids and/or aminoguanidine and; b) Guanylyl cyclase inhibition by MB. As the NO synthesis inhibition is associated to tissue necrosis and adverse hemodynamic effects and its clinical use was associated with high mortality, the second option using MB is safer and more rational. The elaboration of this text was motivated to suggest the guanylyl cyclase inhibition by MB as vasoplegic circulatory shock therapeutical target.
authors.affiliation: Cardiovascular and Endothelium Function Laboratory from the Surgical Research Division, Ribeirão Preto Faculty of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. prbevora@netsite.com.br
authors.forename: P R B
authors.initials: PR
authors.lastname: Evora
authors.forename: F
authors.initials: F
authors.lastname: Viaro
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D008751:Methylene Blue / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D012769:Shock / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D006162:Guanylate Cyclase; D008751:Methylene Blue