Is nitric oxide released in oleic acid lung injury?
Inhibitors of endothelium-derived nitric oxide synthesis or activity have been reported to enhance hypoxic vasoconstriction in isolated lung preparations. We hypothesized that methylene blue, a guanylate cyclase inhibitor, and N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, would increase pulmonary vascular tone and improve gas exchange in anesthetized and ventilated (inspired O2 fraction 0.4) dogs with oleic acid (OA) lung injury. Mean pulmonary arterial pressure-(Ppa) flow (Q) relationships (generated by a manipulation of venous return, which was increased by opening a femoral arteriovenous bypass or decreased by inflating an inferior vena cava balloon) and gas exchange (evaluated by arterial blood gases and SF6 intrapulmonary shunt determinations) were investigated before and after OA (0.06 ml/kg i.v.) and again after solvent (n = 8), methylene blue (8 mg/kg i.v., n = 10), or N omega-nitro-L-arginine (40 mg/kg i.v., n = 8) in a randomized order. OA administration induced pulmonary hypertension, decreased arterial PO2, and increased intrapulmonary shunt. After OA, solvent had no effect on pulmonary hemodynamics and gas exchange. Both methylene blue and N omega-nitro-L-arginine further increased Ppa at all levels of Q. Only methylene blue, however, improved gas exchange after OA (arterial PO2 from 71 +/- 6 to 89 +/- 12 Torr and intrapulmonary shunt from 44 +/- 6 to 34 +/- 6%, both P < 0.02). These results suggest that nitric oxide is released during OA lung injury and modulates pulmonary hypertension. Whether nitric oxide impairs the regulation of gas exchange in OA lung injury remains uncertain, however.
Leeman
M
M
Laboratory of Cardiovascular and Respiratory Physiology, Erasme University Hospital, Brussels, Belgium.
De Beyl
V Z
VZ
Gilbert
E
E
Mélot
C
C
Naeije
R
R
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism*; D008751:Methylene Blue / Q000494:pharmacology; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009829:Oleic Acids; D011651:Pulmonary Artery / Q000378:metabolism; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D013459:Sulfur Hexafluoride / Q000097:blood
D009829:Oleic Acids; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006162:Guanylate Cyclase; D008751:Methylene Blue; D013459:Sulfur Hexafluoride