Clozapine Directly Relaxes Bovine Retinal Arteries

Abstract

Purpose: 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 μM) 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.

KEYWORDS:

• clozapine
• glaucoma
• retinal vasculature
• vasodilation