CALCITONIN GENE-RELATED PEPTIDE INCREASES BLOOD-FLOW AND POTENTIATES PLASMA-PROTEIN EXTRAVASATION IN THE RAT KNEE-JOINT

1 The effects of calcitonin gene-related peptide (CGRP) and other vasoactive mediators of inflammation on blood flow in the synovial vessels and plasma protein extravasation into the knee (femoro-tibial) joint of the pentobarbitone-anaesthetized rat were measured. 2 Changes in synovial blood flow were estimated by xenon-133 clearance from the synovial cavity. CGRP (0.1 pmol and 10 pmol) and prostaglandin E1 (PGE1; 3 pmol and 300 pmol) significantly increased clearance from the knee joint measured 5 min after intra-articular injection. Substance P (10 pmol) had no effect on synovial blood flow. 3 Intra-articular perfusion of the rat knee with CGRP at concentrations up to 0.1 mM, or PGE1 at concentrations up to 10-mu-M, did not increase plasma extravasation into the synovial cavity measured by accumulation of intravenously injected I-125-albumin in the perfusate. 4 Plasma extravasation into the knee was significantly increased by infusion of bradykinin (0.1-mu-M), 5-hydroxytryptamine (1-mu-M) and histamine (0.1 mM), compared with the contralateral joints in the same animals which were perfused with Tyrode solution. 5 Perfusion of the knee joint with substance P did not specifically induce I-125-labelled albumin accumulation in the synovial cavity even at doses that had systemic effects as observed by marked plasma extravasation into other tissues. 6 The increase in plasma extravasation induced by histamine (0.1 mM) was potentiated by co-infusion with CGRP (0.1-mu-M) and PGE1 (3-mu-M). However the response to a submaximal dose (0.1-mu-M) of bradykinin, which induced similar plasma extravasation to histamine (0.1 mM), was not increased by co-infusion with CGRP or PGE1. 7 These results show that CGRP is a potent vasodilator in the rat knee. CGRP released from sensory nerves may act synergistically with mediators of increased vascular permeability to modify the inflammatory response in this site.