Inhaled nitric oxide does not alter endotoxin-induced nitric oxide synthase activity during rat lung perfusion.
Nitric oxide (NO) has been demonstrated to decrease its own synthesis in tissue preparations. We tested the hypothesis that endogenous NO synthesis induced by lipopolysaccharides (LPS) would be decreased by exogenous NO during isolated lung perfusion. Rats were pretreated with either saline or LPS 48 h before lung harvest. Endogenous NO synthase activity was measured as conversion of L-[14C]-arginine to L-[14C]citrulline during 90 min of perfusion. NO (100 ppm) was added to the ventilating gas during perfusion of lungs from one group of control or LPS-treated rats. A second group of control or LPS-treated rats was exposed chronically to 100 ppm NO for the 48 h before lung harvest, in addition to receiving 100 ppm NO added to the ventilating gas during lung perfusion. We conclude that conversion of L-[14C]arginine to L-[14C]citrulline was minimal in control lungs and increased in response to LPS pretreatment. NO added to the ventilating gas for the 90 min of ex vivo perfusion did not alter the rate of L-[14C]citrulline production. In vivo exposure to 100 ppm NO for 48 h did not alter the induction of inducible NO synthase activity as measured during ex vivo lung perfusion. This indicates that inhaled NO does not exert negative-feedback inhibition on inducible NO synthase in the ex vivo rat lung.
Kurrek
M M
MM
Department of Anesthesia, Massachusetts General Hospital, Boston 02114, USA.
Castillo
L
L
Bloch
K D
KD
Tannenbaum
S R
SR
Zapol
W M
WM
D000280:Administration, Inhalation; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005246:Feedback / Q000502:physiology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D009566:Nitrates; D002956:Citrulline; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D001120:Arginine; D019001:Nitric Oxide Synthase