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 investi gated by using models of experimental burn to evaluate severity from the as pect of vascular permeability. Thermal injuries were produced in the murine right ear by pinching with a pair of preheated tweezers. Immediately there after, 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 indicato r of inflammation. Vascular hyperpermeability was suppressed by the adminis tration of nitric oxide synthase inhibitors. LNAME not only suppressed vasc ular hyperpermeability in thermal injuries in a dose-dependent manner but w as also effective with either prophylactic or therapeutic administration. A lthough aminoguanidine also suppressed the inflammatory response, it had no effect on the early inflammatory phase. Nitric oxide synthase is well know n to have two types of isozymes. Aminoguanidine, an inhibitor specific to i nducible nitric oxide synthase, suppressed the late phase 6 h after injury, suggesting that inducible nitric oxide synthase is involved in inflammator y responses of thermal injuries. These results also demonstrated that induc ible nitric oxide synthase-like protein stained the burned region immunohis tochemically. Therefore, both types of enzymes mediating nitric oxide affec t inflammatory responses, i.e., vascular hyperpermeability, and their regul ation may lead to the development of new therapy for thermal injuries. (C) 2001 Academic Press.