AT(1) receptor antagonism enhances angiotensin-II-facilitated carrageenan-induced paw edema

Recent studies have demonstrated that the renin-angiotensin system (RAS) pa rticipates in the processes of inflammation. An active component of this sy stem, angiotensin II (Ang II), differentially regulates the production of o xyradicals, nitric oxide, prostaglandins, platelet-activating factors and b radykinins by acting through AT(1) or AT(2) receptor subtypes. Many of the physiological actions of Ang II mediated through AT(1) and AT(2) receptors are opposite and thereby show physiological antagonism to each other. In th e present study, we evaluated the effect of locally administered Ang II, th e ACE inhibitor captopril and the AT(1) receptor antagonist losartan in the carrageenan model of acute inflammation. Local administration of losartan (10-50 mug/paw) or Ang II (0.2-1 mug/paw) alone did not induce inflammation , but significantly enhanced the carrageenan-induced edema in a dose-depend ent manner. Coadministration of subeffective doses of losartan (10 mug/paw) and Ang II (0.2 mug/paw) significantly potentiated the carrageenan-induced inflammation. In conclusion, the present study predicts that Ang II might be formed locally during carrageenan-induced acute inflammation. Potentiati on of the Ang II effect in carrageenan-induced inflammation by losartan mya be mediated through over-stimulation of unblocked AT(2) receptors or due t o stimulation of inflammatory pathways by unknown mechanisms. (C) 2000 Prou s Science. All rights reserved.