PLASMA-PROTEIN EXTRAVASATION INTO THE RAT KNEE-JOINT INDUCED BY CALCITONIN-GENE-RELATED PEPTIDE

In previous experiments, intra-articular administration of calcitonin gene-related peptide (CGRP) failed to elicit plasma protein extravasat ion into synovial fluid. In the present study, using a sensitive techn ique to assay protein in synovial fluid, intra-articular perfusion of CGRP (10(-6) M) was found to produce protein extravasation which was s ustained throughout the period of infusion. Both lower (10(-7) M) and higher (10(-5) M) concentrations of CGRP failed to produce extravasati on. This failure at the highest concentration of CGRP was the likely c onsequence of a significant fall in arterial blood pressure which occu rred with administration of CGRP at this concentration. In the presenc e of arterial hypotension induced by an alpha-adrenoceptor antagonist, 10-(6) M CGRP failed to produce extravasation. Plasma extravasation i nduced by CGRP was a specific effect and not merely a consequence of i ts potent vasodilator properties as similar vasodilator responses indu ced by a B-adrenoceptor agonist failed to induce protein leakage. Thes e findings indicate that CGRP can alter blood vessel permeability and therefore could additionally contribute to neurally mediated inflammat ory responses.