The role of nitric oxide in the responses of equine digital veins to vasodilator and vasoconstrictor agents.
Isolated equine digital veins were examined in vitro to study the importance of the endothelium in the responses to both vasodilator and vasoconstrictor agents and to characterise the endothelial-derived mediators involved. Carbachol (Cch; 1 microM) and bradykinin (Bk; 1 nM) caused relaxation of U44069-induced tone by 79.5 +/- 0.35% and 73.7 +/- 4.0% respectively. Mechanical removal of the endothelium completely prevented relaxant responses to Cch and to Bk showing they were mediated by the endothelium. Treatment of veins with NG-nitro-L-arginine methyl ester (L-NAME; 30 and 300 microM) inhibited vasorelaxant responses to both Cch and Bk whereas the cyclooxygenase inhibitor, ibuprofen (10 microM) had no inhibitory effect. The inhibitory action of L-NAME on the relaxations produced by Cch was partly reversed by L-arginine (3 and 10 mM). Cch-relaxations were potentiated in the presence of super oxide dismutase (15 units/ml) and inhibited by methylene blue (10 microM). The vasorelaxant effects of ATP (0.01 microM to 0.1 mM) were not dependent on the presence of the endothelium and the selective P2y receptor agonist, 2-methylthio-ATP proved to be ineffective as a vasodilator. Removal of the endothelium did not enhance the vasoconstrictor effects of the alpha 1 adrenoceptor agonist phenylephrine (0.01 microM to 0.1 mM) and treatment with L-NAME (300 microM) did not change the vasoconstrictor responses to 5-HT (1 nM to 10 microM) or the alpha 2 adrenoceptor agonist BHT-920 (1 nM to 1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
Elliott
J
J
Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
Bryant
C E
CE
Soydan
J
J
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply; D006736:Horses / Q000502:physiology*; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects / Q000502:physiology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D002217:Carbachol; D001120:Arginine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007052:Ibuprofen