We examined the vasoconstrictive actions of neuropeptide Y (NPY) in the intact medial collateral ligament (MCL) of normal and anterior cruciate ligament (ACL) -deficient rabbit knees. Blood flow to the surgically exposed MCL was measured using high-resolution laser speckle imaging (LSI) before and after topical administration of NPY and the α₁-adrenoreceptor agonist phenylephrine. In control rabbit knees, dose-dependent vasopressor responses were significantly greater than those in ACL-deficient knees, where there was little or no vasoconstrictor response. We conclude that chronic ACL deficiency markedly changes the vascular physiology and pharmacology of the surrounding articular tissues.

To determine the effect of chronic ACL-deficiency on the physiologic responses to the potent sympathetic vasoconstrictor NPY.

Abrogation of the vasoconstrictor response to both NPY and phenylephrine indicates that chronic ACL deficiency induces major changes in the vascular physiology of associated articular tissues.

This study is the first to examine the vasoregulatory role of NPY in the MCL of unstable knee joints using LSI.

In control rabbits, topical administration of NPY produced dose-dependent vasopressor responses (maximal effect at 10⁻¹⁰mol NPY). In ACL-transected knees there was little or no response to NPY (Figure 1). BIBP 3226 (selective NPY-Y1 receptor antagonist) did not affect the constrictor response to NPY in normal tissue, indicating that a receptor other than Y-1 mediates the response.

Many neuropeptides participate in the post-traumatic inflammatory response. The sympathetic-derived NPY helps regulate inflammatory responses, is a vasoconstrictor and stimulates angiogenesis. Rupture of the ACL induces inflammation, hyperaemia and angiogenesis in the MCL. These changes in vascular physiology induced us to study the effect of ACL-deficiency on the actions of NPY in the MCL.

Unoperated control (n=6) and 6-week ACL-transected (n=5) adult rabbits were used. Under anaesthesia, the MCL was surgically exposed and tissue blood flow was measured in real time using LSI as various doses and combinations of NPY, phenylephrine, and BIBP 3226 were administered topically.

Possible causes of the reduced vasoconstrictive response to both NPY and phenylephrine in the MCL after 6wk of ACL-deficiency include change in the distribution or functionality of their specific receptors or inactivation of the associated down stream signalling pathways.

Funding: This work was supported by funding from the CIHR and the Alberta Heritage Foundation for Medical Research.

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