Anaphylactic shock can be defined as an acute syndrome, and it is the most severe clinical manifestation of allergic diseases. Anaphylactoid reactions are similar to anaphylactic events but differ in the pathophysiological mechanism. Nitric oxide (NO) inhibitors during anaphylaxis suggest that NO might decrease the signs and symptoms of anaphylaxis but exacerbate associated vasodilation. Therefore, blocking the effects of NO on vascular smooth muscle by inhibiting the guanylate cyclase (GC) would be a reasonable strategy. This study aimed to investigate the effects of NO/cGMP pathway inhibitors methylene blue (MB), N o -nitro-L-arginine methyl ester hydrochloride (L-NAME), and indigo carmine (IC) in shock induced by compound 48/80 (C48/80) in rats. The effect was assessed by invasive blood pressure measurement. Shock was initiated by C48/80 intravenous bolus injection 5 min before (prophylactic) or after (treatment) the administration of the inhibitors MB (3 mg/kg), L-NAME (1 mg/kg), and IC (3 mg/kg). Of the groups that received drugs as prophylaxis for shock, only the IC group did not present the final systolic blood pressure (SBP) better than the C48/80 group. Regarding shock treatment with the drugs tested, all groups had the final SBP similar to the C48/80group. Altogether, our results suggested that inhibition of GC and NO synthase in NO production pathway was not sufficient to revert hypotension or significantly improve survival.

In vitro studies have demonstrated organophosphate‐mediated vasodilator effects, suggesting that organophosphates may have peripheral activity independent of acetylcholinesterase inhibition. To evaluate the effect of the organophosphate malathion, on the reactivity of isolated rat aorta as well as to explore the mechanisms involved in this response, including the role of nitric oxide (NO) and prostacyclin (PGI2). The study protocol included two methods: in vitro vascular reactivity and flow cytometry (using DAF‐FM DA dye). In rat thoracic aorta segments pre‐constricted with phenylephrine (Phe), malathion induced vasodilation in arteries with endothelium. Acetylcholine‐mediated vasodilatation was not affected when incubate with malathion. Malathion‐mediated vasodilation was blocked by L‐NAME a non‐specific nitric oxide synthase inhibitor and/or indomethacin, an unspecific cyclooxygenase inhibitor. In thoracic aortas rings, with endothelium, Phe promoted dose‐dependent contraction, which was reduced by malathion. In rings with endothelium incubated with malathion and the two blockers, the Phe contraction, was 100% restored. The role of NO was confirmed using flow cytometry. Malathion causes endothelium‐dependent relaxation mediated synergistically by NO (cGMP pathway) and PGI2 (cAMP pathway) that would be a preventive mechanism against spasm and thrombosis. Research support FAEPA.

A Deus por ser meu suporte espiritual.Ao meus pais, Ademir e Sueli, pela formação pessoal, por me mostrar a importância do estudo, pelo apoio e incentivo para nunca desistir e sempre querer mais.Ao meu esposo Reginaldo, por todo incentivo e apoio nas horas boas e ruins, pelo suporte dentro do laboratório nos finais de semana, por cuidar de tudo na minha ausência e sempre incentivar a busca pelos meus objetivos. Às minhas irmãs, Ísis e Ariadne, que mesmo longe sempre me incentivaram. À família Fagundes, que escolhi fazer parte, Dna Maria, Roger, Fabiana, Fernando, Flávio, sobrinhas Beatriz, Emanuelly e Lorena, pelas palavras de carinho, ajuda e momentos de descontração. Aos primos Claudinei e Vanessa, que mesmo longe foram minha maior torcida.Ao Dr Paulo Evora, pelos ensinamentos e incentivo a dar sempre um passo além, por fazer possível a conquista de mais um objetivo e sempre me cobrar por mais um "paper". À Profa. Dra. Andrea Carla, que antes de ser minha orientadora é uma amiga.Obrigado por toda ajuda possível e impossível para concluir este trabalho, pelas conversas dentro e fora do laboratório e por me mostrar o que é ter amor pela ciência. À Luíza, que chegou no laboratório para estudar e acabou se tornando uma amiga, me ajudando e tornando os dias mais fáceis dentro do laboratório.Ao Willian, por dividir os momentos de frustação ou euforia durante o desenvolvimento deste trabalho.