NITRIC OXIDE IN SEPSIS FROM DEFICIENCY TO OVERPRODUCTION

C Păun, A Ciocănea
2008 unpublished
The presence of NO in blood is important to regulate the vasomotor tonus and the blood flux, and to inhibit the adhesion of leukocytes and of plakets and to modulate the coagulation activity. The proofs suggest that sepsis is associated with: rapid lowering of the ecNOS function with altered relaxation derived from endothelium; increase of the iNOS function which is delayed with a few hours, associated with a modified response of the smooth muscle to vasoconstrictors and vasoplegia. Keywords:
more » ... plegia. Keywords: nitric oxide, severe sepsis, overproduction deficiency. Rezumat: Prezenţa în sânge a NO este importantă pentru reglarea tonusului vasomotor, a fluxului sanguin pentru inhibarea adeziunii leucocitare şi plachetare şi pentru modularea activităţii coagulării. Dovezile sugerează că sepsisul este asociat cu: scăderea rapidă a funcţiei ecNOS cu relaxare derivată din endoteliu alterată, o creştere întârziată cu câteva ore a expresiei NOS asociată cu un răspuns modificat al muşchiului neted la vasoconstrictori şi vasoplegie. Cuvinte cheie: oxid, nitric, sepsis sever, deficienţă de nefroproducţie The Nitric Oxide (NO) is physiologically produced by ecNOS (endothelial NO constitutive syntax). Its presence in the blood flux is important not only for it regulates the vasomotor tonus and the blood flux, but it also inhibits the adhesion of leukocytes and of plakets, as well as it modulates the coagulation activity. Sepsis is associated with a rapid lowering of the ecNOS function with altered relaxation derived from endothelium, with a delayed (of few hours) increase of the inducible NOS function (iNOS), associated with an alteration of the response of the smooth muscles to vasoconstrictors and vasoplegia. The use of the NOS inhibitors restores the response to vasoconstrictors and vasoplegia but it cannot restore the relaxation derived from endothelium: the normalization of the blood pressure is associated with an increased risk of the flux lowering, with the increase of the adhesion of leukocytes and of plakets and the increase of the coagulation activation and organs injury. The clinical research reported the benefic effects of the iNOS inhibition on the homodynamic status but also the undesirable effects, such as: the increase of the pulmonary artery pressure and the augmentation of the organs injuries, as well as the increase of mortality. The negative effects of the NOS inhibitor regarding the septic shock may be related to the absence of the improvement of the ecNOS function, as well as other NO proprieties suppressed during sepsis, such as: the bacterial activity, the modulation of the activated coagulation and the inhibition of the adhesion of leukocytes and of plakets. Endothelium, which could be found in the circulatory system, is a very specialized tissue, involved in the modulation of the immune responses and the increase of the vascular cells and in the regulation of the haemostatic, inflammatory and vasoactive agents' level (1). The endothelium releases the tissue hormones (autacoids) which decisively affect the vascular tonus and the placket function. Many of the relaxing autacoids derived from endothelium were described and characterized-for example: prostacyclin, and the strong vasodilatator compound-the nitric oxide (NO). NO is synthesized in picomolar concentrations (Figure no.
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