Effects of inhaled NO and inhibition of endogenous NO synthesis in oxidant-induced acute lung injury.
Inhaled nitric oxide (NO) decreases pulmonary arterial pressure (Ppa) and improves oxygenation in the adult respiratory distress syndrome. Endogenous NO can modulate the development of acute tissue injury. We investigated the effects of inhaled NO and of inhibition of endogenous NO synthase in oxidant-induced acute lung injury in the isolated buffer-perfused rabbit lung. A rapid (45 min) and a more gradual (3 h) model of oxidant-induced acute lung injury were developed using the production of superoxide free radicals from the reaction of purine with low and high doses of xanthine oxidase, respectively. The effects of rapid injury included increases in Ppa, precapillary pulmonary vascular resistance, capillary filtration coefficient (Kfc), and lung weight. In the gradual-injury model, only lung weight and Kfc increased. Pretreatment with inhaled NO (90-120 ppm) prevented the rise in Ppa and precapillary pulmonary vascular resistance in the rapid-injury model and prevented elevation of Kfc in the gradual-injury model. Pretreatment with an inhibitor of endogenous NO synthase (NG-nitro-L-arginine methyl ester) resulted in increased pulmonary capillary pressure and postcapillary pulmonary vascular resistance in the rapid-injury model and increased peak Ppa, pulmonary capillary pressure, and pulmonary vascular resistance in the gradual-injury model. These data suggest that in oxidant-induced acute lung injury 1) inhaled NO may attenuate increases in capillary permeability and 2) endogenous NO may function as a modulator of pulmonary vascular tone without affecting capillary permeability.
Kavanagh
B P
BP
Department of Anesthesia, Stanford University Medical Center, California 97305-5117.
Mouchawar
A
A
Goldsmith
J
J
Pearl
R G
RG
D000280:Administration, Inhalation; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D066298:In Vitro Techniques; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000008:administration & dosage / Q000096:biosynthesis* / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D016877:Oxidants / Q000633:toxicity*; D011652:Pulmonary Circulation / Q000187:drug effects; D011687:Purines / Q000633:toxicity; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects; D014969:Xanthine Oxidase / Q000633:toxicity
D016877:Oxidants; D011687:Purines; D009569:Nitric Oxide; D001120:Arginine; D014969:Xanthine Oxidase; D019331:NG-Nitroarginine Methyl Ester