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The effect of topical diltiazem on ocular hypertension induced by water loading in rabbits

https://doi.org/10.1016/S0306-3623(98)00196-7Get rights and content

Abstract

The aim of this work was to assess the effect of topical diltiazem on the ocular hypertension induced by water loading in rabbits. The effect of three different concentrations of diltiazem on the intraocular pressure rise produced by oral administration of tap water (60 ml/kg) was tested in groups of nine or ten rabbits each. When applied at the lowest concentration studied, topical diltiazem was found to enhance the intraocular pressure rise after water loading. In contrast, when applied at the highest concentration, diltiazem counteracted the ocular hypertension caused by water loading. Although diltiazem, and probably other calcium channel blockers, may be useful in the management of ocular hypertension, the data obtained suggest that these drugs may have complex actions on aqueous humor dynamics; therefore further studies in animal models for glaucoma should be carried out before their clinical evaluation in humans.

Section snippets

Materials and methods

Experiments were carried out in male albino New Zealand rabbits, weighing 3.2–5.0 kg, that had previously been trained to be handled and restrained in boxes in the laboratory environment. Animals were deprived of water and food for 24 h before each experiment. Intraocular pressure was measured with a manual applanation tonometer (KOWA HA-1) that was calibrated by direct manometry in anesthetized rabbits. Immediately before each study, calibration was checked according to the instructions of the

Results

In the control group, a statistically significant rise in intraocular pressure was found between 30 and 90 min after water loading, a maximum 4.67 ± 0.71 mm Hg increase being observed at 60 min (Fig. 1).

In rabbits receiving 2.75 × 10−3 M diltiazem, water loading produced an increase in intraocular pressure that became statistically significant at 15 min after water loading and lasted 90 min (Fig. 1), a maximum 6.70 ± 0.62 mm Hg elevation being recorded at 30 min. When these data are compared

Discussion

Studies in dogs and men have revealed that the sequence of events that results in the intraocular pressure rise after water loading is precipitated by a reduction in blood osmolality (Galin et al., 1961). Such a reduction would generate an osmotic gradient between blood and aqueous humor and thus a passive flow of water into the eye. In addition, a decrease in the outflow facility of the aqueous humor, likely due to a mechanical obstruction of the outflow by hydration of the trabecular meshwork

Summary

Although there has been a recent interest in the potential role of calcium channel blockers in the treatment of ocular hypertension and low-tension glaucoma, little well-designed studies have been done to examine the ocular actions of these drugs before their clinical application. The aim of the present work was to assess the effect of topical diltiazem on the ocular hypertension induced by water loading in rabbits. This test is considered a useful procedure for the screening of antiglaucoma

Acknowledgments

This research work has been carried out with the aid of a grant from the Universidad del Paı́s Vasco. J. Melena was supported by a fellowship from the Gobierno Vasco (Spain).

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