title: Effects of endotoxin and influence of cyclooxygenase-2 on β-adrenergic mediated relaxation in isolated equine digital artery.
abstract: The effects of endotoxin on β-adrenergic-mediated relaxation were investigated in the equine digital artery (EDA). Possible involvement of cyclooxygenase-2 (COX-2) in endotoxin-induced effects and basal EDA β-adrenoceptor functionality was also evaluated. Endothelium-intact (e(+)) and/or -denuded (e(-)) EDA rings were incubated overnight with lipopolysaccharide (LPS), LPS+NS398 (selective COX-2 inhibitor) or NS398 alone. Vessel rings were then mounted in organ baths and relaxant responses to isoproterenol (ISOP) recorded on U44069-induced pre-contraction. Response to ISOP was further evaluated in either incubated or freshly isolated (e(-)) rings acutely exposed to NS398. Fresh and incubated (e(-)) EDAs were also analysed for COX-2 expression by Western blotting. LPS caused endothelium-dependent enhancement of β-adrenergic mediated relaxation. NS398 did not reverse endotoxin effects, suggesting that COX-2 did not have a mediating role. In the absence of LPS, NS398 significantly increased ISOP-induced relaxation. This finding, together with immunoblot detection of COX-2 in both fresh and incubated (e(-)) vessels, revealed the existence of a constitutive COX-2 exerting tonic inhibitory modulation on EDA β-adrenergic-mediated relaxation. The results support the possible role of endotoxin in the vascular disturbances associated with equine laminitis. Moreover, the involvement of COX-2 in the physiological regulation of EDA tone warrants further clinical investigation into the efficacy and safety of selective COX-2 inhibitors on digital circulation in horses.
authors.affiliation: Department of Veterinary Public Health, Division of Veterinary Pharmacology and Toxicology, University of Bari, Str. Prov. per Casamassima km 3, 70010 Valenzano (BA), Italy. Electronic address: c.zizzadoro@veterinaria.uniba.it.
authors.forename: C
authors.initials: C
authors.lastname: Zizzadoro
authors.affiliation: Department of Veterinary Public Health, Division of Veterinary Pharmacology and Toxicology, University of Bari, Str. Prov. per Casamassima km 3, 70010 Valenzano (BA), Italy.
authors.forename: M
authors.initials: M
authors.lastname: Caruso
authors.affiliation: Department of Veterinary Public Health, Division of Veterinary Pharmacology and Toxicology, University of Bari, Str. Prov. per Casamassima km 3, 70010 Valenzano (BA), Italy.
authors.forename: C
authors.initials: C
authors.lastname: Putignano
authors.affiliation: Department of Veterinary Public Health, Division of Veterinary Pharmacology and Toxicology, University of Bari, Str. Prov. per Casamassima km 3, 70010 Valenzano (BA), Italy.
authors.forename: G
authors.initials: G
authors.lastname: Crescenzo
authors.affiliation: Department of Veterinary Public Health, Division of Veterinary Pharmacology and Toxicology, University of Bari, Str. Prov. per Casamassima km 3, 70010 Valenzano (BA), Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ormas
authors.affiliation: Department of Veterinary Public Health, Division of Veterinary Pharmacology and Toxicology, University of Bari, Str. Prov. per Casamassima km 3, 70010 Valenzano (BA), Italy.
authors.forename: C
authors.initials: C
authors.lastname: Belloli
mesh_terms: D000818:Animals; D001158:Arteries; D015153:Blotting, Western / Q000662:veterinary; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D005534:Foot Diseases / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary*; D006724:Hoof and Claw / Q000098:blood supply*; D006734:Horse Diseases / Q000378:metabolism / Q000503:physiopathology*; D006736:Horses; D066298:In Vitro Techniques; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism* / Q000502:physiology; D012044:Regression Analysis; D013449:Sulfonamides / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D009578:Nitrobenzenes; D011943:Receptors, Adrenergic, beta; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C044101:endotoxin, Escherichia coli; D051546:Cyclooxygenase 2