Article

Effects of nitric oxide synthase inhibitors on vascular hyperpermeability with thermal injury in mice.

Department of Plastic and Reconstructive Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, 216-8511, Japan.
Nitric Oxide (Impact Factor: 3.27). 09/2001; 5(4):334-42. DOI: 10.1006/niox.2001.0350
Source: PubMed

ABSTRACT The role of nitric oxide and related synthase in thermal injury was investigated by using models of experimental burn to evaluate severity from the aspect of vascular permeability. Thermal injuries were produced in the murine right ear by pinching with a pair of preheated tweezers. Immediately thereafter, Evans blue dye was intravenously administered, and the mice injured with burns were sacrificed at various times. The burned ears were collected and hydrolyzed, and the level of extracted dye was measured as an indicator of inflammation. Vascular hyperpermeability was suppressed by the administration of nitric oxide synthase inhibitors. LNAME not only suppressed vascular hyperpermeability in thermal injuries in a dose-dependent manner but was also effective with either prophylactic or therapeutic administration. Although aminoguanidine also suppressed the inflammatory response, it had no effect on the early inflammatory phase. Nitric oxide synthase is well known to have two types of isozymes. Aminoguanidine, an inhibitor specific to inducible nitric oxide synthase, suppressed the late phase 6 h after injury, suggesting that inducible nitric oxide synthase is involved in inflammatory responses of thermal injuries. These results also demonstrated that inducible nitric oxide synthase-like protein stained the burned region immunohistochemically. Therefore, both types of enzymes mediating nitric oxide affect inflammatory responses, i.e., vascular hyperpermeability, and their regulation may lead to the development of new therapy for thermal injuries.

1 Bookmark
 · 
64 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The title molecular salt, (E)-2-(1-phenylethylidene) hydrazinecarboximidamide nitrate hemimethanol C9H13N4(+)·NO3(-)·0.5CH4O, was synthesized and characterized by elemental analysis, FT-IR and NMT spectroscopies, and single-crystal X-ray diffraction technique. Quantum chemical calculations were performed to study the molecular and spectroscopic properties of the title compound, and the results were compared with the experimental findings. The calculated results show that the optimized geometry can well reproduce the crystal structure parameters, and the theoretical vibrational frequencies and GIAO (1)H and (13)CNMR chemical shifts show good agreement with experimental values. The dipole moment, linear polarizability and first hyperpolarizability values were also computed. The linear polarizabilities and first hyper polarizabilities of the studied molecule indicate that the compound is a good candidate of nonlinear optical materials. On the basis of the thermodynamic properties of the title compound at different temperatures have been calculated, revealing the correlations between standard heat capacities (C) standard entropies (S), and standard enthalpy changes (H) and temperatures.
    Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy 05/2013; 114C:175-182. · 1.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neutrophils and monocytes/macrophages (MMs) play important roles in the development of cell-mediated delayed type hypersensitivity (DTH). However, the dynamics of neutrophils and MMs during the DTH reaction and how the immunosuppressant rapamycin modulates their behavior in vivo are rarely reported. Here, we take advantage of multi-scale optical imaging techniques and a footpad DTH reaction model to non-invasively investigate the dynamic behavior and properties of immune cells from the whole field of the footpad to the cellular level. During the classic elicitation phase of the DTH reaction, both neutrophils and MMs obviously accumulated at inflammatory foci at 24 h post-challenge. Rapamycin treatment resulted in advanced neutrophil recruitment and vascular hyperpermeability at an early stage (4 h), the reduced accumulation of neutrophils (> 50% inhibition ratio) at 48 h, and the delayed involvement of MMs in inflammatory foci. The motility parameters of immune cells in the rapamycin-treated reaction at 4 h post-challenge displayed similar mean velocities, arrest durations, mean displacements, and confinements as the classic DTH reaction at 24 h. These results indicate that rapamycin treatment shortened the initial preparation stage of the DTH reaction and attenuated its intensity, which may be due to the involvement of T helper type 2 cells or regulatory T cells.
    Theranostics 01/2014; 4(2):201-14. · 7.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A gas mediator, nitric oxide, is converted into peroxynitrite in the presence of superoxide anion. Peroxynitrite is a potent oxidant, which injures various tissues and organs by nitration of tyrosine residue in protein and enhances the inflammatory response in the prolonged phase. In this study, the authors investigated the relationship between peroxynitrite-mediated tissue nitration and tissue damage with thermal injury using an experimental burn model. The content of nitrotyrosine in the burned tissue significantly increased 1 to 6 h after injury. The nitrotyrosine content in the burned ear significantly decreased with 100 mg/kg of LNAME administration. Vascular hyperpermeability was also significantly suppressed in the iNOS antibody immunoneutralized mice 6 h after injury. There was a positive correlation between the severity of tissue damage, an indicator of which is the increase in the weight of the burned ear along with the development of edema after injury, and the concentration of nitrotyrosine in the wound tissues. Nitrotyrosine-like immune reactants were also diffusely detected in the burned region and the surrounding areas. These results indicate that peroxynitrite is produced in the surrounding burned region and a reaction of nitration of tissue tyrosine is involved with tissue damage at the burn wound. Therefore, to prevent the systemic vascular hyperpermeability and tissue damage in a large area burn or severe burn patients, the administration of NOS inhibitors or radical erasers may be easy to manage generally by inhibition of peroxynitrite formation.
    European Journal of Plastic Surgery 12/2007; 30(4):177-182.

Similar Publications