Effects of Nilvadipine, Nicardipine and Verapamil on Acute Rise of Aqueous Flare Induced by Iris Photocoagulation or Intravenous Lipopolysaccharides in Pigmented Rabbits

Abstract

The effects of nilvadipine, nicardipine and verapamil on the acute rise of aqueous flare induced by argon laser photocoagulation of the iris or by intravenous injection of lipopolysaccharides (LPS, 0.5 µg/kg) were investigated in pigmented rabbits. Nilvadipine, nicardipine and verapamil were injected intravenously. Aqueous flare was measured with a laser flare cell meter. Following photocoagulation, aqueous flare increased, reached its maximum at 45–75 min and then decreased. After administration of LPS, aqueous flare increased, reached its maximum at 4 h and then returned to baseline levels at about 24 h. Flare reactions were inhibited by nilvadipine in a dose-dependent manner. The elevations were maximally inhibited by nilvadipine 30 min before photocoagulation or intravenous LPS. Two hundred micrograms per kilogram of nilvadipine inhibited 81% of photocoagulation-induced flare elevation, while the same dose of nicardipine and verapamil inhibited 19 and 9% of the elevation, respectively. The same dose of nilvadipine inhibited 51% of LPS-induced flare elevation, while the same dose of nicardipine and verapamil inhibited 6 and 4% of the elevation, respectively. In conclusion, nilvadipine inhibited the experimental elevation of aqueous flare more effectively than did nicardipine and verapamil.

Effect of Topical Iganidipine on Experimental Elevation of Aqueous Flare Induced by Prostaglandin E₂ and EP Agonists in Pigmented Rabbits

“…We further reported that nilvadipine inhibited iris photocoagulation-induced flare elevation more effectively than did nicardipine [6]. Oyanagui and Sato [9] reported that nilvadipine inhibited ischemic and carrageenan paw edema.…”

“…Thus, some calcium channel blockers reportedly have anti-inflammatory actions. However, not all calcium channel blockers inhibit the acute rise of aqueous flare induced by PGE 2 in pigmented rabbits: verapamil did not inhibit flare elevation [6]. Iganidipine is reported to have calcium-channel-blocking activity [1].…”

“…Studies from our laboratory have previously reported that two applications of prostaglandin E 2 (PGE 2 ) reproducibly induced aqueous flare elevation in the same eye at 1-week intervals [3,4] and that intravenous injection of certain calcium channel blockers (nilvadipine and nicardipine) inhibited the experimental elevation of aqueous flare in pigmented rabbits [5,6]. We further studied the effect of highly selective agonists for prostaglandin E 2 receptor subtypes (EP1, EP2, EP3 and EP4) on the blood-aqueous barrier in pigmented rabbits and found that ONO-AE1-259-01 (EP2 agonist) and ONO-AE1-392 (EP4 agonist) induced aqueous flare elevation, while ONO-DI-004 (EP1 agonist) and ONO-AE-248 (EP3 agonist) had almost no effect [7].…”

Calcium channel blocker nilvadipine, but not diltiazem, inhibits ocular inflammation in endotoxin-induced uveitis

“…4), suggesting that the antiinfl ammatory effects of nilvadipine on the eye resulted from the inhibition of infl ammation-related molecules. Although a previous report 47 showed an inhibitory effect of nilvadipine on anterior-chamber infl ammation in a rabbit EIU model, the mechanism of its action remains to be elucidated. The present study further unraveled its antiinfl ammatory effect on the retina together with underlying molecular mechanisms.…”

Effect of Topical Betaxolol on the Acute Rise of Aqueous Flare Induced by Highly Selective Agonists for Prostaglandin E₂ Receptor Subtypes in Pigmented Rabbits

“…We have previously reported that PGE 2 -induced flare elevation was inhibited by nilvadipine and nicardipine (calcium channel blockers) [5,6]. Betaxolol is reported to have calcium-channel-blocking activity [7].…”