title: The Gatekeepers in the Mouse Ophthalmic Artery: Endothelium-Dependent Mechanisms of Cholinergic Vasodilation.
abstract: Cholinergic regulation of arterial luminal diameter involves intricate network of intercellular communication between the endothelial and smooth muscle cells that is highly dependent on the molecular mediators released by the endothelium. Albeit the well-recognized contribution of nitric oxide (NO) towards vasodilation, the identity of compensatory mechanisms that maintain vasomotor tone when NO synthesis is deranged remain largely unknown in the ophthalmic artery. This is the first study to identify the vasodilatory signalling mechanisms of the ophthalmic artery employing wild type mice. Acetylcholine (ACh)-induced vasodilation was only partially attenuated when NO synthesis was inhibited. Intriguingly, the combined blocking of cytochrome P450 oxygenase (CYP450) and lipoxygenase (LOX), as well as CYP450 and gap junctions, abolished vasodilation; demonstrating that the key compensatory mechanisms comprise arachidonic acid metabolites which, work in concert with gap junctions for downstream signal transmission. Furthermore, the voltage-gated potassium ion channel, Kv1.6, was functionally relevant in mediating vasodilation. Its localization was found exclusively in the smooth muscle. In conclusion, ACh-induced vasodilation of mouse ophthalmic artery is mediated in part by NO and predominantly via arachidonic acid metabolites, with active involvement of gap junctions. Particularly, the Kv1.6 channel represents an attractive therapeutic target in ophthalmopathologies when NO synthesis is compromised.
authors.affiliation: Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Manicam
authors.affiliation: Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Staubitz
authors.affiliation: Institute of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Brochhausen
authors.affiliation: Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Franz H
authors.initials: FH
authors.lastname: Grus
authors.affiliation: Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Gericke
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology; D051667:Kv1.6 Potassium Channel / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009880:Ophthalmic Artery / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001685:Biological Factors; D018678:Cholinergic Agents; D051667:Kv1.6 Potassium Channel; D026902:Potassium Channel Blockers; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D000109:Acetylcholine
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