Pharmacological investigation of vascular smooth muscle which affect ocular circulation.

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Various anti-glaucoma agents is now available for the treatment of open-angle glaucoma. These drugs are considered to reduce intraocular pressure. Though it is generally accepted that increased intraocular pressure is a major risk factor in glaucoma, the role of the vascular factor is also considered to be important in the pathogenesis of optic nerve damage and visual field loss, especially in patients with normal tension glaucoma. The question of whether these drugs have any effect on ocular blood flow has been studied by many investigators by means of labeled microsphere method or laser speckle microcirculation analyzer. In an attempt to clarify the mechanisms involved in the effectiveness of these drugs on the ocular circulation, we have investigated the pharmacological properties and effects of these drugs on rabbit ciliary arterial smooth muscle in vitro using isometric tension recording methods.Phenyleptirine dose-dependently contracted ciliary artery smooth muscle and bunazosin … More (1muM) shifted this dose-response curve to the right. On the other hand, isoproterenol had no effect up to the concentration of 1 mM.Electrical field stimulation evoked contraction which was mediated by adrenergic nerve fibres. In addition, field stimulation also evoked relaxation when ciliary artery was pre-contracted by histamine. This relaxation was mediated by Nitric Oxide which may be released from non-adrenergic, non-cholinergic nerve terminals. Pilocarpine relaxed this muscle dose-dependently which is due to the release of NO from vascular endothelium. Betaxolol and timolol could directly relax rabbit ciliary artery in vitro in at relatively high concentrations, and relaxation is not due to NO released from the preparation. Presumably, this relaxation occurs through action similar to Ca antagonists. However, the clinical importance of this effect is not yet clarified. Carteolol had no relaxant effect in vitro. Unoprostone also relaxed this muscle, however, this relaxation is not mediated by NO, CGRP or Prostaglandins. This action was not seem to mediated by Ca antagonistic action as well. The mechanisms of relaxing action of unoprostone was not yet clear. Less