Effect of potassium channel openers on intraocular pressure in rabbits.

Sir,

Glaucoma is a slowly progressive optic neuropathy characterized by high intraocular pressure (IOP) that can result in temporary or permanent impairment of vision. It is categorized as open angle or chronic glaucoma and closed angle or acute glaucoma. Worldwide, it is the second leading cause of blindness that affects one in 200 people aged 50 years and one in 10 over the age of 80 years.[1]

Prevention/control of raised IOP is the primary goal in the management of glaucoma. Modern medicine either decrease production of aqueous humour or facilitate outflow and prevent damage to retinal ganglion cells. Topically administered drugs act on the aqueous humour dynamics to reduce the IOP by different mechanisms. Various group of drugs like beta blockers, adrenergic and cholinergic agonists, prostaglandin analogues, carbonic anhydrase inhibitors, calcium channel blockers (CCBs), etc., are used for the treatment of glaucoma.[2]

Potassium channel openers (PCOs) are used along with CCBs in angina, hypertension, congestive heart failure, bronchial asthma, etc. Antiglaucoma activity of CCBs is well documented.[3] Hence, it was hypothesized that PCOs might have antiglaucoma activity similar to CCBs. The present study was therefore undertaken to evaluate the effect of PCOs on IOP and compare it with CCBs.

A total of 24 adult albino rabbits (2.5-3 kg) were divided into three groups of eight each. Glaucoma was induced by using IOP recovery model, as described by Chiang et al.,[4] after the approval of Institutional Animal Ethics Committee. After recording baseline IOP, 10 ml of hypertonic saline was infused through the marginal ear vein at the rate of 1 ml/min with the help of automatic infusion pump for producing fall of IOP. Both eyes were anesthetized by using 2% xylocaine. The recovery of IOP in three groups was recorded at every 20 minutes after instilling normal saline (group-I), diltiazem 0.5% (group-II), and nicorandil 1% (group-III) with the help of Schiotz tonometer, till normal baseline values were obtained. Antibacterial eye drops were instilled after each recording.

The results showed that in all 3 groups, the mean baseline IOP was 18.2 mmHg in each group. After injecting hypertonic saline, it decreased in all the three groups to 7.22, 7.0, and 7.1 mmHg, respectively. Recovery to mean baseline IOP occurred in 120 ± 5.34 minutes in the control group, whereas in diltiazem-treated group, recovery of IOP to mean baseline was delayed, i.e., in 240 ± 5.34 minutes and in nicorandil-treated group, IOP returned to mean baseline much earlier, i.e., in 100 ± 5.34 minutes.

In this study, it was hypothesized that PCOs also act through voltage-dependent calcium channels and might have hypotensive effect on aqueous humour dynamics in rabbits similar to CCBs. The study showed a significant (P<00.1) delay in recovery of IOP to baseline in rabbits treated with diltiazem that was in accordance to study reported earlier.[5] However, it was also observed that unlike CCBs recovery to mean baseline, IOP occurred much earlier with PCOs [Table 1]. Hence, it was concluded that the PCOs do not have hypotensive effect on aqueous humour dynamics.

Table 1

Measurement of intraocular pressure at different time intervals in rabbits treated with diltiazem and nicorandil