Comparison of the effects of adrenergic agonists and α‐, β₁‐, β₂‐antagonists on the intraocular pressure and adenylate cyclase activity in the ciliary processes of the rabbit

Abstract

The hypotensive effect of different adrenergic agonists and antagonists were screened both in normo- and hypertensive rabbit eyes. The drugs were applicated topically and intraocular pressure (IOP) was monitored constantly with a manometric method. Subsequently the inhibitory effect of the antagonists on isoproterenol-stimulated adenylate cyclase activity in the ciliary processes was analyzed in vitro. In normotensive eyes agonist isoproterenol (beta) and antagonists labetalol (alpha beta), metoprolol (beta 1) and acebutolol (beta 1) decreased significantly IOP. In hypertensive eyes only isoproterenol and labetalol decrease IOP markedly. Timolol (beta) did not decrease IOP, although it inhibited adenylate cyclase activity as actively as labetalol. The other antagonists showed no inhibitory effect on in this respect. The results indicated that alpha-activity (labetalol, alpha beta) seems to potentiate the beta-activity (timolol, beta) in decreasing IOP. Whether this alpha-effect is a presynaptic effect (adrenergic denervation destroys it) is not yet clear. Similarly the beta 1-effect (metoprolol), without affecting adenylate cyclase activity, decreased IOP as well. This might be due to pre-synaptic release of endogenous transmitter(s) which in turn stimulate post-synaptic adenylate cyclase and induce the decreased IOP. Besides this, the possible role of blood vessels and CNS must also be kept in mind.