title: Endothelial mechanisms underlying responses to acetylcholine in the horse deep dorsal penile vein.
abstract: This study evaluates the mechanisms underlying endothelium-dependent responses to acetylcholine in horse deep dorsal penile veins. Acetylcholine-induced relaxation was abolished by endothelium removal, the soluble guanylyl cyclase-inhibitor, and the nitric oxide (NO) synthase inhibitors. Acetylcholine-induced relaxation was inhibited by high K+ concentrations and blockade of large-conductance Ca(2+)-activated potassium (BK(Ca)) channels, and voltage-dependent potassium (K(v)) channels. Relaxations were unaffected by a small-conductance K(Ca) (SK(Ca)) channel blocker, or an ATP-sensitive potassium (K(ATP)) channel blocker. Relaxation in response to a NO donor was unaffected by K(Ca) channel blockers, but inhibited by high K+ concentrations and a K(v) channel blocker. In the presence of a NO synthase inhibitor, acetylcholine-induced contractions were inhibited by a cyclooxygenase blocker and abolished by endothelial removal. The contractile response was competitively inhibited by muscarinic receptor antagonists, high affinity M1 and M3 antagonists, while the M2 antagonist had no effect. The pharmacological profile suggests that acetylcholine contraction is mediated by muscarinic M1 receptors. Our findings indicate that acetylcholine-induced relaxation in the horse deep dorsal penile vein is essentially mediated by NO, acting via the cGMP-dependent pathway and opening of K+ channels. The contraction elicited by acetylcholine is prostanoid-mediated and induced by endothelial muscarinic M1 receptor activation.
authors.affiliation: Sección Departamental de Fisiología, Facultad de Farmacia, Universidad Complutense, UCM, 28040 Madrid, Spain.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Martínez
authors.forename: Dolores
authors.initials: D
authors.lastname: Prieto
authors.forename: Medardo
authors.initials: M
authors.lastname: Hernández
authors.forename: Luis
authors.initials: L
authors.lastname: Rivera
authors.forename: Paz
authors.initials: P
authors.lastname: Recio
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
authors.forename: Sara
authors.initials: S
authors.lastname: Benedito
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006736:Horses; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010413:Penis / Q000098:blood supply*; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D012977:Sodium Nitrite / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects / Q000502:physiology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011810:Quinoxalines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D019335:Nitroarginine; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D012977:Sodium Nitrite; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin