Retinal concentration and protective effect against retinal ischemia of nilvadipine in rats.
OBJECTIVE
Several calcium entry blockers have neuroprotective effects on cellular damage in the brain induced by ischemia. The purpose of this study was to determine whether nilvadipine (NID) crosses the blood-retinal barrier, and if so, whether it can then protect the photoreceptors against retinal ischemia-reperfusion injury.


METHODS
Rats received an intramuscular injection of 1 mg/kg of NID and nifedipine (NIF), and the retinal and serum concentrations were measured. Ischemia was induced by raising the intraocular pressure for 45 minutes. Twenty-four hours after the reperfusion, the number of TUNEL positive cells and retinal ganglion cells (RGCs) were counted, and the thickness of the retina was measured.


RESULTS
After 60 minutes, the concentration of NID, but not NIF, was higher in retina than in the serum. The number of TUNEL-positive cells was fewer and the reduction in the number of RGCs and the thickness of retina was less in the eyes that had received NID than controls.


CONCLUSIONS
The findings show that NID has high permeability to retina compared with NIF, which has less fat solubility than NID, and neuroprotective effect to retinal cells. NID might be useful for the treatment of glaucoma or other retinal diseases that have some relation to apoptosis.
Uemura
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Department of Ophthalmology, International Medical Center of Japan, Tokyo, Japan.
Mizota
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D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D001813:Blood-Retinal Barrier / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002199:Capillary Permeability / Q000187:drug effects; D002452:Cell Count; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D007273:Injections, Intramuscular; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D014018:Tissue Distribution
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; C035100:nilvadipine; D009543:Nifedipine