Effects of nitric oxide synthase inhibitors on vascular hyperpermeability with thermal injury in mice.
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.
Inoue
H
H
Department of Plastic and Reconstructive Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, 216-8511, Japan. h2inoue@marianna-u.ac.jp
Ando
K
K
Wakisaka
N
N
Matsuzaki
K
K
Aihara
M
M
Kumagai
N
N
D000818:Animals; D002056:Burns / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000293:injuries* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005070:Evans Blue; D006146:Guanidines / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000175:diagnosis; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000187:drug effects
D004791:Enzyme Inhibitors; D006146:Guanidines; D007527:Isoenzymes; D005070:Evans Blue; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester