EFFECTS OF INTERACTIONS OF NATURALLY-OCCURRING NEUROPEPTIDES ON BLOOD-FLOW IN THE RAT KNEE-JOINT

1 Changes of blood flow in the rat knee joint, measured by laser Doppler flowmetry, were produced by topical application of naturally-occurring neuropeptides to the joint capsule. 2 Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) all produced dose-dependent transient vasodilatation of the rat knee joint microvasculature. NKB showed significantly smaller vasodilator responses compared to SP and NKA which were similar in their potencies. 3 Calcitonin gene-related peptide (CGRP) produced dose-dependent vasodilatation which was more pronounced than that produced by the neurokinins. The rank order of potency was: CGRP>SP = NKA>NKB. The vasodilator effect of CGRP was also more prolonged and this extended phase was abolished by co-administration of SP. 4 Cross-tachyphylaxis was not observed with the different neurokinins, but SP and NKA showed novel antagonistic effects on NKB-induced vasodilatation. 5 Co-administration of 1 nmol of the specific NK1 receptor antagonist, CP-96345, with 1 nmol of each of the neurokinins produced significant inhibition of the vasodilator response to SP but did not affect vasodilator responses to NKA and NKB. Co-administration of CP-96345 with the neurokinins plus superfusion of the rat knee joint with a solution containing 0.1 mm CP-96345 further reduced the vasodilator responses to SP but again the vasodilator responses to NKA and NKB were not significanly altered. 6 The results suggest that multiple neurokinin receptor types may be present in the rat knee joint which could mediate the vasodilator responses of the different neurokinins. Co-release of neuropeptides from sensory nerve endings in the rat knee joint may have inter-regulatory actions on their individual responses on the microvasculature.