SPATIAL HETEROGENEITY OF THE EFFECTS OF CALCITONIN-GENE-RELATED PEPTIDE (CGRP) ON THE MICROVASCULATURE OF LIGAMENTS IN THE RABBIT KNEE-JOINT

1 Experiments were performed in anaesthetized rabbits to examine the e ffects of calcitonin gene-related peptide (CGRP) and the CGRP antagoni st CGRP8(8-37) on blood flow to the medial collateral ligament of the knee joint. 2 Topical application of CGRP (10(-13) to 10(-9) mol) to t he exposed external surface of eight knee joints resulted in dose-depe ndent dilatation of vessels in both the ligament and the joint capsule . The magnitude of this response varied significantly in different reg ions of the medial collateral ligament, with the 10(-9) mol dose of CG RP giving the maximum response (101.5+/-25.3% increase) at the femoral insertion site of the medial collateral ligament and lowest (23.1+/-8 .8%) at the tibial insertion site. 3 Topical application of CGRP(8-37) (0.1, 1 and 10 nmol) produced dose-dependent constriction of vessels in the ligament and the joint capsule in five knees, with a trend towa rds the greatest effect occurring at the femoral insertion site (45.8/-8.1% reduction in blood flow). With the 10 nmol dose, the vasoconstr ictor response at the femoral insertion site differed significantly (P <0.05) from the responses obtained at the tibial insertion and joint c apsule sites.4 Topical application of CGRP(8-37) (0.1, 1 and 10 nmol) to four chronically denervated knees produced substantially smaller va soconstrictor responses at all sites. At the femoral insertion site, w here 10 nmol CGRP(8-37) normally produces a 45.8+/-8.1% reduction in b lood flow (n=8), ten days following denervation this response was redu ced to 6.5+/-6.1%, this difference being significant (P=0.01). 5 Adren aline was applied topically to augment blood vessel tone, in order to establish how effectively co-administration of CGRP would offset this increase in tone. Adrenaline (10(-10) mol) produced vasoconstriction a t all sites (n=6). In the capsule this vasoconstriction was virtually abolished when CGRP (10(-9) mol) was co-administered with adrenaline b ut in the ligament vasodilatation occurred at all sites. This vasodila tation was significantly greater at the femoral insertion site compare d to the tibial insertion and mid ligament sites (P<0.05 for both) and the capsule (P<0.01). 6 Topical application of substance P (10(-10) o r 10(-9) mol) failed to elicit dilatation of ligament blood vessels. 7 These results suggest that endogenous CGRP may play an important role in regulating blood flow to different structures in and around the kn ee joint.