Role of prostaglandins and nitric oxide in acute inflammatory reactions in guinea‐pig skin

Open Access
Publisher Website
Google Scholar
Abstract
Oedema formation in skin is dependent on a synergism between mediators that increase vascular permeability and mediators that enhance local blood flow. Leukocyte accumulation is also enhanced by mediators that increase local blood flow. In this study, we have investigated whether nitric oxide (NO), an important endogenous vasodilator, could modulate oedema formation and leukocyte accumulation in guinea‐pig skin. Local administration of the NO synthesis inhibitor, NG‐nitro‐l‐arginine methyl ester (l‐NAME), dose‐dependently inhibited the oedema formation induced in response to intradermal injection of bradykinin or histamine. l‐NAME, but not NG‐nitro‐d‐arginine methyl ester (d‐NAME), also inhibited oedema formation in response to i.d. injection of platelet‐activating factor (PAF), zymosan‐activated plasma (ZAP) and in a passive cutaneous anaphylactic (PCA) reaction. N‐iminoethyl‐l‐ornithine (l‐NIO) was less effective and about 100 times less potent than l‐NAME in inhibiting bradykinin‐induced oedema formation. The cyclo‐oxygenase inhibitor, ibuprofen, had little effect on oedema responses induced by bradykinin, PAF and in a PCA reaction. On the other hand, histamine‐induced oedema formation was significantly suppressed by ibuprofen. The inhibition by l‐NAME of bradykinin‐induced oedema formation was reversed by co‐injection of sodium nitroprusside (SNP) or prostaglandin E1 (PGE1). L‐NAME inhibited 111In‐eosinophil and 111In‐neutrophil accumulation induced by i.d. injection of ZAP. 111In‐eosinophil accumulation induced by PAF and in the PCA reaction was also inhibited by l‐NAME but not by d‐NAME. Co‐injection of SNP or PGE1, reversed the inhibition by l‐NAME of ZAP‐induced oedema formation and 111In‐neutrophil accumulation. SNP, but not PGE1, also reversed the effects of l‐NAME on ZAP‐induced 111In‐eosinophil accumulation. l‐NAME caused a significant decrease in basal cutaneous blood flow when injected alone or with bradykinin. Again, SNP or PGE1 reversed the effects of l‐NAME suggesting that the inhibitory action of l‐NAME on oedema formation and cell accumulation was due to an inhibition of vasodilator tone in the microcirculation. Thus, it appears that in guinea‐pig skin the inhibition of the production of endogenous NO inhibits both leukocyte accumulation and oedema formation induced by different mediators of inflammation. Since administration of l‐NAME also causes a local decrease in basal blood flow, we suggest that this is the mechanism by which it exerts anti‐inflammatory effects in this model.