Nicardipine modification of endothelin-1 effects on visual evoked potential

Endothelin-1 (ET-1), a vascular endothelium-derived peptide, regulates microcirculation by modulating Ca2+ ion channels. Intravitreally injected ET-1 constricts retinal vessels and reduces blood flow in the optic nerve capillaries. We examined the antagonistic effect of a calcium-ion channel blocker, nicardipine, on ET-1 effects on visual evoked potential (VEP). ET-1 (10(-6); 10 microL) was injected into the posterior vitreous of rabbit eyes. Intravenous nicardipine (20 micrograms/kg) was also given, and VEP was monitored for 2 hours following injection. Thirty minutes after injection, ET-1 had reduced VEP amplitude to 42.6% of the baseline level. The reduction effect continued for the remainder of the study. Nicardipine suppressed the ET-1-induced reduction of VEP amplitude (P < 0.05, Scheffe). The vasospasm produced by ET-1, which reduces the VEP amplitude, involves the CA2+ ion channel. Since nicardipine interferes with the activity of ET-1, we believe that Ca2+ channel blockers can be useful in the treatment of ischemic retinal and optic nerve disorders that are related to abnormal ET-1 production.