The effects of endotoxin on b-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 b-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 b-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 b-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.

Effects of endotoxin and influence of cyclooxygenase-2 on beta-adrenergic mediated relaxation in isolated equine digital artery

ZIZZADORO, CLAUDIA;CRESCENZO, Giuseppe;BELLOLI, Chiara
2011

Abstract

The effects of endotoxin on b-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 b-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 b-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 b-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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/133323
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 4
  • ???jsp.display-item.citation.isi??? ND
social impact