Dorzolamide induces vasodilatation in isolated pre-contracted bovine retinal arteries

The effect of the carbonic anhydrase inhibitor dorzolamide on vascular smooth muscle in pre-contracted bovine retinal arteries was examined. Ring segments of retinal arteries were placed in a small vessel myograph for measurement of contractile activity. The arteries were placed in a physiological saline solution. Vasoconstriction was induced by either 124 mM KCl (0.90 +/- 0.46 mN, n = 34), 10(-4) M prostaglandin F-2alpha (1.72 +/- 0.84 mN, n = 10) or 10(-6) M norepinephrine (0.78 +/- 0.47 mN, n = 6). Both KCl and prostaglandin F-2alpha caused steady repeatable contractions but norepinephrine caused a single phasic contraction. The effect of the carbonic anhydrase inhibitor, dorzolamide on the vasoconstriction was examined. Dorzolamide, if added to the bath when the vasoconstriction had reached a maximum steady level, caused a highly significant relaxation (vasodilatation) of the arteries. This action of dorzolamide occurred irrespective of which agent was used to induce vasoconstriction. Similar results were obtained in experiments were Hepes buffer was used instead of CO2/bicarbonate buffer. The vasodilatation induced by dorzolamide was stable as long as the drug remained in the bath, and was reversible. These results show that dorzolamide causes a vasodilatation of retinal arteries, pre-contracted by three different mechanisms by direct action and presumably independent of changes in extracellular pH. (C) 2003 Elsevier Ltd. All rights reserved.