General Pharmacology: The Vascular System
General papersThe effect of topical diltiazem on ocular hypertension induced by water loading in rabbits
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).
References (27)
- et al.
Sustained reduction of intraocular pressure in humans with the calcium channel blocker verapamil
Am J Ophthalmol
(1988) - et al.
Dihydropyridine-sensitive Ca2+ spikes and Ca2+ currents in rabbit ciliary body epithelial cells
Exp Eye Res
(1994) - et al.
Studies on the mechanism of the water drinking test
Am J Ophthalmol
(1961) - et al.
Alterations of intracellular calcium in human non-pigmented ciliary epithelial cells of the eye
Exp Eye Res
(1989) - et al.
Electrophysiological properties of cultured human trabecular meshwork cells
Exp Eye Res
(1994) - et al.
The effect of a calcium-channel blocking agent on intraocular pressure
Am J Ophthalmol
(1983) - et al.
Calcium channel blockers in the management of low-tension and open-angle glaucoma
Am J Ophthalmol
(1993) - et al.
Color Doppler ultrasound analysis of ocular circulation after topical calcium channel blocker
Am J Ophthalmol
(1995) - et al.
Adrenergic drugs and intraocular pressuresuppression of ocular hypertension induced by water loading
Exp Eye Res
(1980) - et al.
The topical application of verapamil and nifedipine lowers intraocular pressure in conscious rabbits
Gen Pharmac
(1993)
Heterogeneous response in calcium signaling by adrenergic and cholinergic stimulation in cultured bovine trabecular cells
Exp Eye Res
Detection and characterization of Ca2+-activated K+ channels in transformed cells of human non-pigmented ciliary epithelium
Curr Eye Res
Dopaminergic involvement in intraocular pressure in the rabbit eye
Ophthalmic Res
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