RELATIONSHIP BETWEEN NITRIC-OXIDE AND PROSTAGLANDINS IN CARRAGEENAN PLEURISY

The correlation between endogenous nitric oxide (NO) generation and pr ostaglandin biosynthesis was studied in rat carrageenin pleurisy induc ed by the injection of 0.2 mt of 1% lambda-carrageenin into the pleura l cavity. The pleural exudate was collected at 4 hr and the amounts of NO2- + NO3- (NOx) and prostaglandin E-2 (PGE(2)) measured. The NOx pr esent in the inflammatory exudate was determined by measuring the NO2- with the Griess reaction, after the reduction of NO3- to NO2- using a cid-washed cadmium powder. PGE(2) was measured by radioimmunoassay. Th e NO synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME; 1-3 -10 mg/kg subcutaneously) reduced NOx by 20 +/- 7%, 41 +/- 6% and 55 /- 9% (P < 0.01) and PGE(2) by 9 +/- 6%, 41 +/- 11% and 74 +/- 9% (P < 0.001). Conversely, L-arginine (300 mg/kg SC) increased NOx by 39 +/- 7% (P < 0.01) and PGE(2) by 78 +/- 6% (P < 0.001). The NO scavenger h aemoglobin (Hb), coinjected into the pleural cavity (3 mg/site) with c arrageenin, produced a parallel inhibition of NOx (65 +/- 16%, P < 0.0 01) and PGE(2) (71 +/- 18%, P < 0.001). The soluble guanylate cyclase inhibitor methylene blue (Mb; 2 mg/site) had no effect. Moreover haemo globin, but not methylene blue, was able to significantly suppress the L-arginine-induced increase of both NOx and PGE(2). In each pleural e xudate, independently from the animal treatment, the amount of NOx was highly correlated to the amount of PGE(2) (r = 0.93, P < 0.001). Thes e results suggest that in rat carrageenin pleurisy the modulation of t he L-arginine:NO pathway results in a parallel modulation of prostagla ndin biosynthesis. The interaction between cyclooxygenase and the NO p athway may represent an important mechanism for the modulation of the inflammatory response. (C) 1998 Elsevier Science Inc.