The role of nitric oxide in the responses of the ovine digital artery to vasoactive agents and modification of these responses by endotoxin and cytokines

Pawson, P., Reid, J. and Nolan, A.M. (2000) The role of nitric oxide in the responses of the ovine digital artery to vasoactive agents and modification of these responses by endotoxin and cytokines. British Journal of Pharmacology, 130(1), pp. 109-117. (doi: 10.1038/sj.bjp.0703286)

Abstract

Laminitis, an important cause of lameness in domestic ungulates, occurs as a result of altered digital perfusion. Endotoxin and cytokines may mediate the vascular derangements observed through alterations in nitric oxide production. In this study, the vascular responses of the isolated ovine digital artery were examined and the influence of endotoxin and cytokines investigated. Neither removal of the endothelium nor incubation with NG-nitro-L-arginine methyl ester (L-NAME, 300 μM) altered the response to phenylephrine (PE, 1 nM to 300 μM). Indomethacin (10 μM) decreased PE log EC50 from −6.22±0.08 to −6.55±0.07. Acetylcholine (1 nM to 1 mM) and bradykinin (BK, 100 pM to 3 μM) induced endothelium-dependent relaxation. Bradykinin-induced relaxation was reduced by L-NAME, Emax falling from −61.7±7.4 to −34.0±2.1%. Addition of indomethacin further reduced BK Emax to −9.6±2.8%. Sodium nitroprusside (1 nM to 300 μM) produced endothelium-independent relaxation that was unaffected by L-NAME or indomethacin. Following a 6 h incubation with endotoxin (3 μg ml−1), arterial responses to PE and BK did not differ from polymyxin B-treated controls (10 μg ml−1). Arteries incubated for 6 h with interferon-γ (IFN-γ, 10 ng ml−1) and tumour necrosis factor-α (TNF-α, 5 ng ml−1) exhibited greater relaxation to BK (Emax−50.0±5.1%) than polymyxin B-treated controls (Emax−33.1±4.0%), but did not differ in their response to PE. Prolonged incubation (16 h) with endotoxin (3 μg ml−1) did not alter the response to PE, however incubation with IFN-γ (10 ng ml−1), TNF-α (5 ng ml−1) and interleukin-1β (20 ng ml−1) for 16 h increased PE log EC50 from −6.44±0.09 to −6.10±0.11. Nitric oxide is an important mediator of endothelium-dependent relaxation in ovine digital arteries but does not modulate PE-induced vasoconstriction. Incubation with cytokines decreased the sensitivity of digital arteries to PE.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Nolan, Professor Andrea and Pawson, Dr Pat and Reid, Professor Jacky
• Authors: Pawson, P., Reid, J., and Nolan, A.M.
• Subjects: S Agriculture > SF Animal culture > SF600 Veterinary Medicine
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: British Journal of Pharmacology
• ISSN: 0007-1188
• Published Online: 29 January 2009