Relationship Between Nitric Oxide and Prostaglandins in Carrageenin Pleurisy

Abstract

The correlation between endogenous nitric oxide (NO) generation and prostaglandin biosynthesis was studied in rat carrageenin pleurisy induced by the injection of 0.2 mL of 1% λ-carrageenin into the pleural cavity. The pleural exudate was collected at 4 hr and the amounts of NO 2 − + NO 3 − (NOx) and prostaglandin E 2 (PGE 2) measured. The NOx present in the inflammatory exudate was determined by measuring the NO 2 − with the Griess reaction, after the reduction of NO 3 − to NO 2 − using acid-washed cadmium powder. PGE 2 was measured by radioimmunoassay. The 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 haemoglobin (Hb), coinjected into the pleural cavity (3 mg/site) with carrageenin, produced a parallel inhibition of NOx (65 ± 16%, P < 0.001) and PGE 2 (71 ± 18%, P < 0.001). The soluble guanylate cyclase inhibitor methylene blue (Mb; 2 mg/site) had no effect. Moreover haemoglobin, but not methylene blue, was able to significantly suppress the l-arginine-induced increase of both NOx and PGE 2. In each pleural exudate, independently from the animal treatment, the amount of NOx was highly correlated to the amount of PGE 2 ( r = 0.93, P < 0.001). These results suggest that in rat carrageenin pleurisy the modulation of the l-arginine:NO pathway results in a parallel modulation of prostaglandin biosynthesis. The interaction between cyclooxygenase and the NO pathway may represent an important mechanism for the modulation of the inflammatory response.