Veterinaria

Plasma and synovial fluid endothelin-1 and nitric oxide concentrations in horses with and without joint disease
Jorge de la Calle, LVM, MS; Daniel J. Burba, DVM; Chidambaram M. Ramaswamy, BVSc, MSc; Giselle Hosgood, BVSc, MS; Jamil Williams, MS, DVM; Casey LeBlanc, DVM; Rustin M. Moore, DVM, PhD
Objective—To compare plasma and synovial fluid endothelin-1 (ET-1) and nitric oxide (NO)concentrations in clinically normal horses and horses with joint disease. Animals—36 horses with joint disease, and 15 horses without joint disease. Procedure—Horses with joint disease were assigned to 1 of the 3 groups (ie, synovitis, degenerative joint disease [DJD], or joint sepsis groups) on the basis of findings on clinical and radiographic examination and synovial fluid analysis. Endothelin-1 and NOconcentrations were measured in plasma from blood samples, collected from the jugular vein and ipsilateral cephalic or saphenous vein of the limb with an affected or unaffected joint, as well as in synovial fluid samples obtained via arthrocentesis from the involved joint. Results—Plasma ET-1 concentrations between affected and unaffected groups were not significantly different. Median concentrationand concentration range of ET-1 in synovial fluid obtained from the joint sepsis group (35.830 pg/mL, 7 .926 to 86.614 pg/mL; n = 7) were significantly greater than values from the synovitis (17 .531 pg/mL, 0.01 to 46.908 pg/mL; 18), DJD (22.858 pg/mL, 0.01 to 49.990 pg/mL; 10), and unaffected (10.547 pg/mL, 0.01 to 35.927 pg/mL; 10) groups. Plasma and synovial fluid NO concentrations betweenaffected and unaffected groups were not significantly different. Conclusions and Clinical Relevance—Endothelin-1 is locally synthesized in the joints of horses with various types of joint disease. Synovial fluid concentrations of ET-1 varied among horses with joint disease, with concentrations significantly higher in the synovial fluid of horses with joint sepsis. These results indicate that ET-1 mayplay a role in the pathophysiologic mechanism of joint disease in horses. (Am J Vet Res 2002;63:1648–1654)

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oint disease is a common clinical condition and a major cause of lameness and loss of performance in

horses.1,2 The concentration of certain inflammatory mediators increases locally in the joints of horses with joint disease.3 Numerous investigations have revealed that there is anincrease in nitric oxide (NO) and endothelin-1 (ET-1) concentrations in serum and synovial fluid of humans with joint disease.4-10, a Nitric oxide is a multifunctional, intercellular, and intracellular messenger molecule that plays a role in a variety of physiologic and pathophysiologic processes.11-17 An increase in NO concentrations in joints may play a role in the development and propagationof joint disease, specifically rheumatoid arthritis in humans4 and osteoarthritis in humans and in other species.4,18 Results of in vitro studies indicate that chondrocytes are capable of synthesizing large quantities of NO in response to cytokines and lipopolysaccharides.19,20 Other studies have detected an increase in concentrations of NO in tissues obtained from joints of dogs affected withosteoarthritis,18 humans affected with rheumatoid arthritis,5 and horses with osteoarthritic joints21 and subchondral cystic lesions.22 Nitric oxide contributes to joint disease by activating metalloproteinases,23 increasing susceptibility to injury by other oxidants,24 decreasing collagen and proteoglycan synthesis,25 reducing expression of interleukin-1 receptor antagonist,26 and chondrocyteapoptosis.27 It has also been reported that NO may stimulate cyclooxygenase-2, resulting in increased prostaglandin production.28 Cyclooxygenase products such as prostaglandin E2 have been shown to be involved in the enzymatic degradation of articular cartilage in horses.3 Endothelin-1 is a 21-amino acid polypeptide that induces potent and sustained vasoconstriction.29 Endothelin-1 was originally...