Inhibition of nitric oxide synthase reduces Sephadex-induced oedema formation in the rat lung: dependence on intact adrenal function.
In the present study we have investigated the effect of L-nitro arginine mono methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase on Sephadex induced inflammation in the rat lung. Instillation of Sephadex into the airways induced an inflammatory reaction characterized by a long-lasting interstitial oedema, measured as an increase in lung weight, and an influx of inflammatory cells into the airways. L-NAME given s.c. prevented the increase in lung weight following Sephadex instillation. The inactive enantiomer D-NAME had no effect, nor did aminoguanidine which indicates that this effect of L-NAME was mediated by inhibition of the constitutive form of NOS. Treatment with L-NAME did not reduce an established oedema. In contrast, L-NAME tended to enhance the influx of oesinophils into the airways of Sephadex-instilled animals. L-NAME did not have any effect on the development of oedema in adrenalectomized rats or in animals where formation of glucocorticosteroids (GCS) was inhibited with metyrapone. L-NAME did not however, increase plasma levels of corticosterone. The present results indicate that, in this model, inhibition of NO-synthesis has marked anti-inflammatory effects. The underlying mechanism is complex but seems not to involve prevention of overproduction of NO.
Andersson
S E
SE
Dept. of Pharmacology, Astra-Draco AB, Lund, Sweden.
Källström
L
L
Malm
M
M
Miller-Larsson
A
A
Axelsson
B
B
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000097:blood; D003911:Dextrans; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007442:Intubation, Intratracheal; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003911:Dextrans; D004791:Enzyme Inhibitors; C025614:sephadex; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone; D008797:Metyrapone