sodium-nitrite and pimagedine

Nitric oxide (NO) is a potent vasodilator that is synthesized by constitutive and inducible isoforms of the enzyme NO synthase (eNOS and iNOS, respectively). The half-life of NO averages only 3 to 4 s in biological fluids, where it is rapidly converted to the stable oxidation products nitrite (NO2-) and nitrate (NO3-). Our objectives were to use 2 commercial kits to measure total plasma NO, as NO2- + NO3-, and to assess plasma NO values during experimental protocols designed to influence NO accumulation in the plasma. One kit employed copper-coated cadmium as a catalyst for reducing NO3- to NO2-; the second kit employed the enzyme NO3- reductase for the same purpose. Both then employed Griess reagent for the colorimetric determination of NO2- as a measure of total plasma NO. Broilers in Experiment 1 were infused i.v. with solutions containing increasing concentrations of sodium NO2-. Broilers in Experiment 2 were injected with 1 mg of lipopolysaccharide (LPS), which is known to stimulate iNOS activity. Both commercial kits successfully detected increases in total plasma NO attributable to ongoing i.v. NO2- infusion or to increased iNOS expression at 5 h after the LPS injection. In Experiment 3, we compared the total plasma NO responses to LPS in the presence and absence of aminoguanidine (AG), a selective inhibitor of iNOS. The AG significantly attenuated the LPS-mediated increase in total plasma NO at 5 h post-injection. In Experiment 4, broilers were infused with sodium nitroprusside (SNP), an exogenous NO donor molecule that previously had been shown to lower the pulmonary arterial pressure in broilers. The SNP infusion did substantially reduce the pulmonary arterial pressure, but an increase in total plasma NO was not detected during the SNP infusion. Overall, NO accumulation in the plasma was successfully detected after sustained infusion of NaNO2 and administration of LPS for 5 h, but biologically effective levels of NO released from SNP were not detected. Therefore, total plasma NO concentrations (assayed as NO2- + NO3-) qualitatively reflect whole-body NO synthesis, but biologically relevant quantities of NO may be produced at levels that cannot be detected by colorimetric assays.

Topics: Animals; Chickens; Colorimetry; Enzyme Inhibitors; Guanidines; Infusions, Intravenous; Kinetics; Lipopolysaccharides; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Nitroprusside; Oxidation-Reduction; Reagent Kits, Diagnostic; Sodium Nitrite

Nitric oxide has many functions in wound healing and metabolism of bone. In the current study the role of nitric oxide on bone healing was investigated. Thirty-six young adult male Sprague-Dawley rats were divided into three groups: control, nitroso-bovine serum albumin, and aminoguanidine. Five millimeter segmental defects were created in the middle of the right femora. A polyethylene plate and screw posts were used for rigid fixation. Demineralized bone matrix served as the graft material in all groups. Nitroso-bovine serum albumin (an active nitric oxide congener) carried by demineralized bone matrix was applied locally at the defect in the nitroso-bovine serum albumin group. Aminoguanidine (an inducible nitric oxide synthase inhibitor) group received oral aminoguanidine treatment. Formation and healing of bone were determined by radiographic and histologic analyses. In comparison to the control group the healing rate was faster in both experimental groups as indicated by radiographic and histologic data. If accompanied by bone graft with a suitable delivery system, nitric oxide may be useful as a therapeutic adjuvant in clinical situations when local formation of bone is needed. Moreover, when combined appropriately, treatment with orthotopic nitric oxide supplementation and systemic inducible nitric oxide synthase inhibition may enhance bone healing.

Topics: Administration, Oral; Administration, Topical; Animals; Bone and Bones; Bone Matrix; Drug Carriers; Femur; Guanidines; Male; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Serum Albumin, Bovine; Sodium Nitrite; Wound Healing

The effects of a range of nitric oxide (NO)-related compounds on histamine release from human basophils and rat peritoneal mast cells were studied. Basal and immunologic histamine releases from human basophils were not affected by N(omega)-nitro-L-arginine, N(omega)-nitro-L-arginine methyl ester, aminoguanidine or methylene blue (all inhibitors of NO production), sodium nitroprusside (an NO donor), L-arginine (a substrate for NO synthase) or D-arginine (the inactive enantiomer of L-arginine). In rat peritoneal mast cells, NO donors such as sodium nitroprusside, sodium nitrite and sodium nitrate, and lipopolysaccharide (an inducer of NO synthase) had little effect on basal histamine release, while 3-morpholino-sydnonimine (SIN-1, an NO donor), L-arginine and D-arginine increased this release by up to threefold. None of the inhibitors of NO production had any striking effect on histamine release induced by anti-rat immunoglobulin E (IgE), compound 48/80, sodium fluoride, phospholipase C, 1,2-dioctanoyl-sn-glycerol or ionophore A23187. However, haemoglobin was found to inhibit histamine release by anti-rat IgE or A23187 by ca. 40%. Alone of the NO donors, low concentrations of L-arginine produced a mild inhibition of histamine release induced by anti-IgE, compound 48/80 and A23187, but not other ligands, while sodium nitroprusside dose-dependently inhibited (by a maximum of ca. 30%) histamine release by anti-rat IgE, sodium fluoride or A23187. Stimulation with a variety of secretagogues or treatment with L-arginine, D-arginine, lipopolysaccharide, SIN-1 or sodium nitroprusside had no effect on NO production. Similarly, L-arginine, D-arginine or sodium nitroprusside did not change intracellular cGMP levels. On the basis of these results, it is suggested that NO does not play a significant role in the modulation of histamine release from human basophils or rat peritoneal mast cells. The effects of L-arginine, D-arginine and sodium nitroprusside may involve mechanisms unrelated to NO.

Topics: Animals; Antibodies; Arginine; Basophils; Calcimycin; Dose-Response Relationship, Drug; Guanidines; Hemoglobins; Histamine; Humans; Immunoglobulin E; Male; Mast Cells; Methylene Blue; Molsidomine; NG-Nitroarginine Methyl Ester; Nitrates; Nitric Oxide; Nitric Oxide Donors; Nitroarginine; Nitroprusside; p-Methoxy-N-methylphenethylamine; Peritoneal Cavity; Rats; Rats, Sprague-Dawley; Sodium Fluoride; Sodium Nitrite