nitroarginine and Hypersensitivity

The aim of this study was to examine the effects of nitric oxide synthase inhibition on antigen- and histamine-induced acute airway reactions, in order to clarify the possible modulating role of NO. Twelve specific-pathogen-free pigs (sensitized with Ascaris suum antigen) were challenged with an antigen aerosol during mechanical ventilation and anaesthesia. Six pigs were pretreated with N(G)-nitro-L-arginine (L-NA, 10 mg x kg(-1)), a NO synthase inhibitor, 30 min before challenge. In separate experiments, seven sensitized pigs received histamine (5 mg) aerosols before and after L-NA treatment. It was found that pretreatment with L-NA resulted in an enhanced airways resistance response to antigen (areas under the curve 0-90 min were (mean+/-SEM) 1,119+/-160 versus 555+/-56 (cmH2O x L(-1) x s(-1) x min for controls, p<0.05 (Mann-Whitney U-test), whereas this response to histamine was not affected by L-NA. Moreover, L-NA pretreatment significantly enhanced total protein (1.85+/-0.43 versus 0.31+/-0.06 g x L(-1), p<0.01) and histamine levels (42.8+/-16.0 versus 2.6+/-0.8 nM, p<0.05) in bronchoalveolar lavage fluid 45 min after antigen challenge. In conclusion, this study showed that N(G)-nitro-L-arginine enhanced reactions occurring during the acute allergic reaction in pigs in vivo. This indicates a protective role of nitric oxide, which might occur through downregulation of histamine release from mast cells rather than a direct bronchodilating effect of nitric oxide.

Topics: Acute Disease; Airway Resistance; Animals; Antigens, Helminth; Ascaris suum; Bronchi; Bronchoalveolar Lavage Fluid; Cardiovascular System; Enzyme Inhibitors; Gases; Histamine; Hydrogen-Ion Concentration; Hypersensitivity; Inflammation Mediators; Lung Compliance; Nitric Oxide Synthase; Nitroarginine; Swine

The sensitivity of animals to endotoxin differs significantly between species. Thus, factors that determine the susceptibility to endotoxin may play important roles in the pathogenesis of septic shock. In order to determine the mechanism responsible for susceptibility to endotoxin, the effect of lipopolysaccharide (LPS) on the circulatory status of Propionibacterium acnes (PA)-sensitized rats was studied. Following the intravenous administration of a low dose of LPS, the arterial blood pressure of PA-treated rats, but not of normal animals, progressively decreased; the PA-sensitized animals died of circulatory shock within 7 h of LPS administration. N omega-nitro-L-arginine (NA) reduced the depressor effect of LPS by an L-arginine-inhibitable mechanism. Administration of LPS markedly increased the level of the inducible type of nitric oxide (NO) synthase in various tissues, including the aorta, of PA-treated rats but not of control animals. LPS also increased plasma levels of nitrate plus nitrite and aortic levels of cGMP. Dexamethasone inhibited the de novo synthesis of NO synthase in the aorta and other tissues and reduced the depressor effect of LPS. These and other findings suggest that induction of nitric oxide synthase in resistant arteries might underlie the pathogenesis of LPS-induced hypotension in PA-sensitized animals and the mechanism responsible for the susceptibility to endotoxin.

Topics: Amino Acid Oxidoreductases; Animals; Aorta; Arginine; Blood Pressure; Cyclic GMP; Dexamethasone; Enzyme Induction; Heart Rate; Hepatectomy; Hypersensitivity; Lipopolysaccharides; Male; Nitrates; Nitric Oxide Synthase; Nitrites; Nitroarginine; Propionibacterium acnes; Rats; Rats, Wistar; Shock, Septic; Splenectomy; Survival Analysis; Tissue Distribution