Constitutive nitric oxide modulates the injurious actions of vasopressin on rat intestinal microcirculation in acute endotoxaemia.
ABSTRACT The administration of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg s.c.) concurrently with Escherichia coli endotoxin (3 mg/kg i.v.) increased vascular permeability and caused mucosal damage in the rat intestine 1 h later. The vasopressin V1 receptor antagonist, [Mca1,Tyr(Me)2, Arg8]vasopressin (0.01-0.2 microgram/kg s.c., 15 min before endotoxin) dose-dependently reduced this damage. These results suggest a beneficial role of NO, counteracting the injurious vascular actions of endogenous vasopressin, in maintaining intestinal mucosal integrity in acute endotoxaemic states.
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ABSTRACT: The influence of endogenous cell .NO production and .NO derived from exogenous sources on oxidant injury to cultured fetal rat lung alveolar epithelium and an animal model of pulmonary oxidant injury was examined. Confluent fetal rat alveolar epithelial cell monolayers were stimulated to produce .NO after treatment with a combination of cytokines (IL-1 beta, TNF-alpha, IFN-gamma), LPS and zymosan-activated serum (CZ). Cell injury, assessed by 14C-adenine release, was significantly increased compared to basal and CZ-induced cells after inhibition of .NO synthesis by L-NMMA. Cell monolayer macromolecule barrier function was determined by the rate of diffusion of 125I-albumin from the apical to basolateral side of monolayers. Following exposure to CZ and/or O2.- generated by xanthine oxidase + lumazine (XO), endogenous cell .NO production and exogenously administered .NO (from .NO donors S-nitrosyl-glutathione and S-nitroso-N-acetylpenicillamine) significantly inhibited the increased monolayer permeability induced by exposure to reactive oxygen species. Furthermore, inhalation of 5-10 ppm of .NO significantly reduced the toxicity of > 95% oxygen to adult rats. We conclude that when cultured pulmonary epithelial cells and lung tissue in vivo are subjected to inflammatory mediators or acute oxidative stress, .NO can play a protective role by inhibiting O2.(-)-dependent toxicity.Free Radical Biology and Medicine 02/1996; 21(1):43-52. DOI:10.1016/0891-5849(95)02226-0
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ABSTRACT: The role of endogenous vasopressin was studied in the development of mucosal erosions induced by haemorrhagic shock in the duodenum of the rat. Ischaemia-reperfusion provoked duodenal haemorrhagic lesions and elevated circulating and intramucosal vasopressin level. This mucosal injury was significantly attenuated by a vasopressin pressor receptor antagonist. Moreover, in the vasopressin-deficient Brattleboro homozygous rat, mucosal injury induced by haemorrhagic shock was also reduced. By contrast, when the vasopressin agonist, lysin-vasopressin, was administered, significant aggravation of ischaemia-reperfusion-induced duodenal mucosal injury was seen. These findings indicate the aggressive role of endogenous vasopressin, via its pressor receptors, in the generation of duodenal mucosal stress erosions in haemorrhagic shock.Inflammopharmacology 12/1996; 4(4):379-385. DOI:10.1007/BF02755790
- Upsala Journal of Medical Sciences 02/1997; 102(3):137-73.