Characterization of agonist-induced endothelium-dependent vasodilatory responses in the vascular bed of the equine digit

Berhane, Y; Bailey, S R; Putignano, C; Elliott, J

Abstract

The role of endothelium-derived relaxing factors was studied in the regulation of vascular responses in the Krebs perfused equine isolated digit. Perfusion pressure was recorded in response to bolus doses of 5-hydroxytryptamine (6 nmol) alone or co-administered with carbachol (CCh; 0.2 mu mol), bradykinin (BK; 0.2 nmol), substance P (SP; 0.2 nmol) or sodium nitroprusside (SNP; 0.2 mu mol). N-omega-Nitro-L-Arginine methyl ester hydrochloride (L-NAME; 300 mu M) caused partial but significant inhibition of CCh-induced vasodilatory response, whereas BK and SP-induced responses were resistant to L-NAME. High potassium (K+, 30 mM) and the cytochrome P-450 (CYP) epoxygenase inhibitor, clotrimazole (10 mu M) plus L-NAME (100 mu M), completely abolished the CCh, BK and SP-induced vasodilatory responses, whereas the response to SNP was unaffected. In contrast, the L-NAME-resistant proportion of CCh, BK and SP-induced vasodilatory response was not inhibited by the highly selective CYP2C9 inhibitor, sulphaphenazole (10 mu M). The cyclo-oxygenase inhibitor, ibuprofen (10 mu M) did not affect the CCh, BK and SP-induced responses. These data demonstrate that CCh, BK and SP-induced relaxation in the equine digit involve a combination of the NO and endothelium-derived hyperpolarizing factor (EDHF) pathways. These results do not support the evidence for the involvement of CYP-derived epoxyeicosatrienoic acids and the exact nature of EDHF in the equine digit remains to be established.

Citation

Berhane, Y., Bailey, S. R., Putignano, C., & Elliott, J. Characterization of agonist-induced endothelium-dependent vasodilatory responses in the vascular bed of the equine digit. Journal of Veterinary Pharmacology and Therapeutics, 31(1), 1-8. https://doi.org/10.1111/j.1365-2885.2007.00912.x

• Journal Article Type: Article
• Deposit Date: Nov 11, 2014
• Journal: Journal of Veterinary Pharmacology and Therapeutics
• Print ISSN: 0140-7783
• Electronic ISSN: 1365-2885
• Publisher: American Academy of Veterinary Pharmacology and Therapeutics
• Volume: 31
• Issue: 1
• Pages: 1-8
• DOI: https://doi.org/10.1111/j.1365-2885.2007.00912.x
• Public URL: https://rvc-repository.worktribe.com/output/1428529
• Additional Information: Corporate Creators : Bari