Characterization of agonist-induced endothelium-dependent vasodilatory responses in the vascular bed of the equine digit.
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 micromol), bradykinin (BK; 0.2 nmol), substance P (SP; 0.2 nmol) or sodium nitroprusside (SNP; 0.2 micromol). N(omega)-Nitro-L-Arginine methyl ester hydrochloride (L-NAME; 300 microm) 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 microm) plus L-NAME (100 microm), 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 microm). The cyclo-oxygenase inhibitor, ibuprofen (10 microm) 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.
Berhane
Y
Y
Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK. yberhane@rvc.ac.uk
Bailey
S R
SR
Putignano
C
C
Elliott
J
J
D000818:Animals; D001158:Arteries / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D006734:Horse Diseases / Q000503:physiopathology; D006736:Horses / Q000502:physiology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin; D013373:Substance P; D002217:Carbachol; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester