AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 1 65-L70, Copyright © 1995 by American Physiological Society
Leukotoxin, 9,10-epoxy-12-octadecenoate causes edematous lung injury via activation of vascular nitric oxide synthase
T. Ishizaki, K. Shigemori, T. Nakai, S. Miyabo, T. Ozawa, S. W. Chang and N. F. Voelkel
Department of Internal Medicine, Fukui Medical School, Japan.
We examined the mechanism of leukotoxin, 9,10-epoxy-12-octadecenoate
(Lx)-induced lung injury in blood-free, physiological salt
solution-perfused rat lungs under constant flow conditions. Mean pulmonary
arterial (Ppa) and pulmonary capillary pressure (Pcap, estimated by the
double-occlusion method), wet lung weight (WLW), pulmonary capillary
filtration coefficient (Kfc), lung perfusate lactate dehydrogenase (LDH)
activity, and nitrite levels were assessed. Bolus injection of Lx (200
microM) caused insidious and significant lung weight gain, which was not
associated with remarkable elevation of Ppa or Pcap but was associated with
an increase of perfusate LDH activity and nitrite levels. Lx (20 microM)
elevated Kfc, indicating that Lx had affected pulmonary vascular
permeability. Because Lx causes endothelium dependent pulmonary
vasodilation, we studied the effect of NG-monomethyl-L-arginine (L-NMMA),
NG-monomethyl-D-arginine (D-NMMA), superoxide dismutase (SOD), human
oxyhemoglobin (oxyHb), and methylene blue (MB) on Lx-induced lung injury.
L-NMMA, SOD, and oxyHb, but not MB or D-NMMA, protected the lungs against
Lx (200 microM)-induced injury. Lx increased pulmonary vascular
permeability and caused lung injury. Because both nitric oxide synthase
inhibitors and SOD inhibited the Lx-induced lung injury, it is possible
that peroxynitrite is involved in the mechanism whereby Lx causes lung
injury.
