Clozapine directly relaxes bovine retinal arteries.
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.
Boussery
Koen
K
Department of Physiology and Pathophysiology, Ghent University, Ghent, Belgium.
Lambrecht
Stijn
S
Delaey
Christophe
C
Van de Voorde
Johan
J
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*
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