Envolvimento do oxido nitrico nas respostas edematogenicas e espasmogenicas induzidas pela bradicinina e histamina

AUTOR(ES)
DATA DE PUBLICAÇÃO

1995

RESUMO

No synthesized from L-arginine, is responsible for various biological effects including oedema formation by plasma protein extravasation (PPE). PPE responses have been measured using local accumulation of intravenously injected 1251-human serum albumin and blood flow by means of a multiple 133 Xenon (Xe) technique in guinea pig skin. L-NAME reduced responses to bradykinin (BK) or histamine and that inhibitory effect was reversed by L-arginine on the response to BK but not on that to histamine. L-arginine alone enhanced the response to BK but inhibited that to histamine. It is therefore possible that NO may play a greater role in the extravasation response to BK than to that induced by histamine. The differential effects of L-NAME and isoprenaline on BK and histamine-induced PPE raise the possibility that BK and histamine may induce vascular permeability via different mechanisms in guinea-pig skin. We also investigated the effect of the amino acids including L-arginine, 0arginine and L-Iysine on airway smooth muscle responsiveness to spasmogen in vitro. Both L-arginine and D-arginine significantly reduced the contractile potency and maximal contractile response to histamine but not to methacholine or potassium chloride in guinea-pig epithelium denuded isolated trachea. In guinea-pig isolated trachea precontracted with histamine, both L-arginine and 0arginine produced a concentration-dependent relaxation. The relaxant response was not significantly altered by epithelium removal or by the presence of LNAME. Thus, very high concentration of arginine non-competitively antagonizes histamine induced contraction of isolated airway preparations that are independent of the generation of nitric oxide and are not dependent on charge, as L-Iysine had no effect. The nitric oxide (NO) synthase inhibitors L-NAME, L-NMMA and L-NO Arg inhibited bradykinin induced PPE when co-injected with the peptide. The inhibitory effect of L-NAME on PPE lasted for 8 hours, whereas its effects on blood flow lasted up to 4 hours, showing that L-NAME is acting by other means other than by only reducing blood flow. In a new series of experiments the nitrovasodilators GTN, SNP and SNAP were tested for their ability to potentiate bradykinin induced PPE. Only SNAP produced significant increases in the BK response. When tested for their ability to increase skin blood flow, SNP, SNAP and PGE2 produced similar increases in basal blood flowwhereas GTN produced smaller responses. The effects of GTN, PGE2 and SNAP on BK induced PPE correlate well with their ability to increase skin blood flow. In contrast, the effect of SNP on mediator induced PPE only becomes evident under conditions where local skin blood flow is reduced e.g. in the presence of L-NAME or phenylephrine. In conclusion (1) arginine appears to have an anti-histaminic effect (2) the effects of NO synthase inhibitors on blood flow does not correlate well with its effects on PPE and (3) the nitrovasodilators utilized have different mechanism of action

ASSUNTO(S)

arginina oxido nitrico permeabilidade fluxo sanguineo

ACESSO AO ARTIGO

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