Effects of beta antagonists on mechanical properties in rabbit ciliary artery

Abstract

Background: We set out to clarify the mechanisms involved in the effectiveness of beta-adrenergic receptor antagonists on the ocular circulation.

Methods: The effects of three beta antagonists, timolol, betaxolol and carteolol, on the isolated rabbit ciliary artery were investigated in vitro using isometric tension recording methods.

Results: Phenylephrine dose-dependently contracted ciliary artery smooth muscle, and bunazosin (1 microM) shifted this dose-response curve to the right. Isoproterenol, on the other hand, had no effect up to the concentration of 1 mM. Betaxolol and timolol had no effect on the ciliary artery. However, carteolol dose-dependently contracted this muscle from a concentration of 1 microM. After precontraction by excess-[K]0 solutions, application of betaxolol or timolol dose-dependently provoked relaxation; the minimum concentration of betaxolol or timolol required to generate the relaxation was 100 microM and 300 microM, respectively. Carteolol did not generate relaxation at concentrations up to 1 mM. After pretreatment with L-NAME (300 microM), the amplitude of relaxation induced by 10 microM carbachol was reduced to 33.0+/-20.2%, while betaxolol- or timolol-induced relaxation was unchanged. Diltiazem (10 microM) induced relaxation which was not inhibited by pretreatment with L-NAME.

Conclusion: Betaxolol and timolol could directly relax rabbit ciliary artery in vitro at relatively high concentrations, and relaxation was 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 clear. Carteolol had no relaxant effect in vitro.