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Characterization of agonist‐induced endothelium‐dependent vasodilatory responses in the vascular bed of the equine digit
Author(s) -
BERHANE Y.,
BAILEY S. R.,
PUTIGNANO C.,
ELLIOTT J.
Publication year - 2008
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2007.00912.x
Subject(s) - vasodilation , chemistry , bradykinin , sodium nitroprusside , epoxygenase , pharmacology , endocrinology , agonist , carbachol , nitric oxide , medicine , arachidonic acid , biochemistry , receptor , enzyme , organic chemistry
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 μmol), bradykinin (BK; 0.2 nmol), substance P (SP; 0.2 nmol) or sodium nitroprusside (SNP; 0.2 μmol). N ω ‐Nitro‐ l ‐Arginine methyl ester hydrochloride (l ‐NAME; 300 μ 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 m m ) and the cytochrome P ‐ 450 (CYP) epoxygenase inhibitor, clotrimazole (10 μ m ) plus l ‐NAME (100 μ 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 μ m ). The cyclo‐oxygenase inhibitor, ibuprofen (10 μ 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.