title: Clozapine directly relaxes bovine retinal arteries.
abstract: OBJECTIVE
  It was suggested that clozapine might be helpful in the development of new antiglaucoma agents, as it combines lowering the intraocular pressure after topical instillation with vasodilation. This study aimed to evaluate and characterize the vasodilatory effect of clozapine in isolated bovine retinal arteries (BRAs).
  
  
  METHODS
  Retinal arteries were isolated from bovine eyes and mounted in the organ bath of a small vessel myograph.
  
  
  RESULTS
  Cumulative addition of clozapine (1 nM to 10 microM) caused a concentration-dependent relaxation of the BRAs. Removal of the endothelium, inhibition of nitric oxide synthase and of soluble guanylyl cyclase reduced the clozapine response, whereas cyclooxygenase inhibition had no influence. A Ca2+ channel activator, a 5-hydroxytryptamine receptor antagonist, and an adenosine receptor antagonist failed in affecting the clozapine-induced relaxations.
  
  
  CONCLUSIONS
  Clozapine relaxes bovine retinal arteries. Endothelium-derived NO seems to be involved, whereas prostanoids, calcium entry blockade, 5-HT7 receptor stimulation, and adenosine receptor stimulation do not.
authors.affiliation: Department of Physiology and Pathophysiology, Ghent University, Ghent, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Boussery
authors.forename: Stijn
authors.initials: S
authors.lastname: Lambrecht
authors.forename: Christophe
authors.initials: C
authors.lastname: Delaey
authors.forename: Johan
authors.initials: J
authors.lastname: Van de Voorde
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002417:Cattle; D003024:Clozapine / Q000494:pharmacology*; D015237:Dinoprost / 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; D008719:Methiothepin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D012161:Retinal Artery / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D002120:Calcium Channel Agonists; D004791:Enzyme Inhibitors; D012702:Serotonin Antagonists; D009569:Nitric Oxide; D008719:Methiothepin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006162:Guanylate Cyclase; D003024:Clozapine