title: Endothelial dysfunction and decreased vascular responsiveness in the anterior cruciate ligament-deficient model of osteoarthritis.
abstract: Chronic inflammation associated with osteoarthritis (OA) may alter normal vascular responses and contribute to joint degradation. Vascular responses to vasoactive mediators were evaluated in the medial collateral ligament (MCL) of the anterior cruciate ligament (ACL)-deficient knee. Chronic joint instability and progressive OA were induced in rabbit knees by surgical transection of the ACL. Under halothane anesthesia, laser speckle perfusion imaging (LSPI) was used to measure MCL blood flow in unoperated control (n = 12) and 6-wk ACL-transected knees (n = 12). ACh, bradykinin, histamine, substance P (SP), and prostaglandin E(2) (PGE(2)) were applied to the MCL vasculature in topical boluses of 100 microl (dose range 10(-14) to 10(-8) mol). In normal joints, ACh, bradykinin, histamine, and PGE(2) evoked a dilatory response. Substance P caused a biphasic response that was dilatory from 10(-14) to 10(-11) mol and constricting at higher doses. In ACL-deficient knees, ACh, bradykinin, histamine, and SP decreased perfusion, whereas PGE(2) had a biphasic response that decreased perfusion at 10(-14) to 10(-11) mol and was dilatory at higher concentrations. Sodium nitroprusside increased perfusion in resting and phenylephrine-precontracted vessels with no significant differences between ACL-transected and control knees. Femoral artery occlusion and release increased perfusion by 74.3 +/- 11.1% in control knees but only by 25.8 +/- 4.4% in ACL-deficient knees. The altered responsiveness of the MCL vasculature to these inflammatory mediators may indicate endothelial dysfunction in the MCL, which may contribute to the progression and severity of OA and to the adaptation of the joint in an altered mechanical environment.
authors.affiliation: University of Calgary, Alberta, Canada T2N 4N1.
authors.forename: Daniel
authors.initials: D
authors.lastname: Miller
authors.forename: Kevin
authors.initials: K
authors.lastname: Forrester
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
authors.forename: Catherine
authors.initials: C
authors.lastname: Leonard
authors.forename: Paul
authors.initials: P
authors.lastname: Salo
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bray
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006940:Hyperemia / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology; D017888:Medial Collateral Ligament, Knee / Q000098:blood supply* / Q000503:physiopathology; D020370:Osteoarthritis, Knee / Q000503:physiopathology*; D011817:Rabbits