The histaminergic control of the iridal vascular tone in rats and its influencing by topical administration of olopatadine and ranitidine

Abstract

Objective. We evaluated the histamine’s role in regulating the iris vasomotricity in rats, using as a research tool topical olopatadine, a selective H1 blocker, which is indicated for the treatment of allergic conjunctivitis and ranitidine, a selective H2 blocker mainly used for the treatment of peptic ulcer disease. Methods. Two groups of six Wistar rats anesthetized with ketamine 200 mg/kg body weight were used. They received distilled water in conjunctival instillations, initially and after 5 minutes, olopatadine 2.5 mmol/ l for the first group, respectively ranitidine 2.5 mmol/ l for the second group. The changes of the iris arteriolar and venular diameters were recorded. Results. Both olopatadine and ranitidine produced statistically significant iridal arteriolar vasoconstriction and ranitidine determined statistically significant venuloconstriction, while distilled water did not produce any statistically significant effect. Conclusions. There is a vasodilator histaminergic tone exerted through the histaminergic H1 and H2 receptors in the iris arterioles and, respectively, through the H2 receptors in the iridal venules. Olopatadine, a topical H1 antagonist used in the treatment of ocular allergies, may interfere with the humoral regulation of the iris arteriolar tone. Ranitidine, an H2 antagonist, decreased the diameter of the iris arterioles and venules, when administered topically in rats.

Histaminergic Control of the Iridal Vasomotricity in Albino Rats

“…The used substances were: Distilled water (Zentiva SA, Romania), Ketamine, 10% solution (CP-Ketamin 10%, CP-Pharma, Germany, veterinary medicine), Olopatadine, ophthalmic solution 1 mg/mL (Opatanol ® 1 mg/mL, ophthalmic drops, Alcon, United Kingdom) -H1 antagonist, Ranitidine, 25 mg/mL solution for injection (Arnetin ® 50 mg/2 mL, solution for injection, Medochemie, Cyprus) -H2 antagonist, Histamine hydrochloride, purity powder > 99% (Sigma). The experimental protocol was described in previously published papers [12]. 15 minutes after the rats were anesthetized with ketamine 10%, we began to record the right eye of each animal.…”

“…The experimental data published so far did not present a complete picture of the effects of histamine on the vasomotricity of the anterior ocular segment, in vivo. Most studies used isolated organ experimental models, and a few in vivo models [1,5,12,20]. However, regarding the role of the histaminergic system on vascular control of the ocular posterior segment, there are some human studies showing the vasodilating effect of histamine through H1 receptors, more in the choroidal territory than in the retinal territory [18,23,26].…”

“…However, regarding the role of the histaminergic system on vascular control of the ocular posterior segment, there are some human studies showing the vasodilating effect of histamine through H1 receptors, more in the choroidal territory than in the retinal territory [18,23,26]. Research regarding the control of the anterior ocular segment vasomotricity, by exogenously administered histamine in conjunctival instillations, is rarely addressed in experimental studies [1,12,18,20]. From an experimental point of view, the Wistar albino rats allow an easy observation of the iridal vessels, in vivo.…”

Novel Insight of Histamine and Its Receptor Ligands in Glaucoma and Retina Neuroprotection

“…Promethazine, an antipsychotic with antihistamine activity, has been shown to produce an idiopathic swelling of the lens that could increase the risk of angle-closure glaucoma. Topical administration of ranitidine produces vasoconstriction in both the arterioles and the venules of the iris, suggesting a predominant role of histamine H 2 R in the vasculature of the iris [52].…”

“…Histamine H 1 Rs are localized on horizontal cells and in a small number of amacrine cells, whereas histamine H 2 Rs appear closely associated with synaptic ribbons inside cone pedicles [41]. Histaminergic H 1 and H 2 receptors in the iris arterioles and H 2 receptors in the iridal venules modulate vascular tone in rats [52]. Moreover, several ocular hypertensive effects have been reported in chronic glaucoma patients following the use of cimetidine and ranitidine, two H 2 R antagonists, for peptic ulcer treatment [53]; on the contrary, recent studies have failed to demonstrate the significant action of topical administered H 2 blockers on IOP in humans [54].…”