Effect of chronic nitric oxide synthesis inhibition on the inflammatory responses induced by carrageenin in rats.
The effect of chronic inhibition of nitric oxide (NO) biosynthesis has been investigated in two models of acute inflammation induced by carrageenin, i.e., paw oedema and pleurisy. Chronic inhibition of NO biosynthesis was achieved by including N omega-nitro-L-arginine methyl ester (L-NAME) in the drinking water to give a dose of approximately 75 mumol/rat/day for 2 and 4 weeks. Control animals received either tap water alone or the inactive enantiomer D-NAME. Since chronic NO inhibition increases blood pressure, rats made hypertensive (2 kidney-1 clip model; 2K-1C) were used to evaluate the effect of hypertension on the carrageenin-induced paw oedema. In a separate set of experiments, L-NAME-treated animals concomitantly received captopril (140 mumol/rat/day) to prevent hypertension. Animals chronically treated with L-NAME (but not D-NAME) for 2 and 4 weeks developed hypertension to the same extent as 2K-1C rats. Carrageenin-induced paw oedema was significantly reduced in animals chronically treated with L-NAME, but not with D-NAME or in 2K-1C rats. Subplantar injection of iloprost completely reversed the inhibition of paw oedema caused by L-NAME. Captopril (140 mumol/rat/day) significantly lowered the high blood pressure levels induced by L-NAME but did not significantly affect the inhibition of paw oedema caused by L-NAME. No changes in vascular permeability, as assessed by Evans blue extravasation, were observed in L-NAME-treated animals. The chronic treatment with L-NAME for 2 and 4 weeks did not inhibit carrageenin-induced leucocyte migration and fluid exudation into the pleural cavity. Although carrageenin-induced paw oedema is reduced in L-NAME-treated rats, this response reflects a decrease in local blood flow rather than an effect on vascular permeability.
Medeiros
M V
MV
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas (SP), Brazil.
Binhara
I M
IM
Moreno Júnior
H
H
Zatz
R
R
De Nucci
G
G
Antunes
E
E
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D002351:Carrageenan; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005070:Evans Blue; D006978:Hypertension, Renovascular / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010998:Pleurisy / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D005070:Evans Blue; D002351:Carrageenan; D001120:Arginine; D002216:Captopril; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester