Reversal of endothelin-1-induced ocular hemodynamic effects by low-dose nifedipine in humans

There is evidence that calcium channel blockers may be useful in patients with normal tension glaucoma and vasospastic reactions. We therefore hypothesized that calcium channel blockers may increase ocular blood flow and that there may be a functional antagonism between endothelin-1 (ET-1) and calcium channel blockers in the ocular vasculature.

This was a randomized, double-blind, three-way crossover study with respect to ET-1 infusions (placebo, 2 ng/kg/min ET-1, and 4 ng/kg/min ET-1) and a randomized double-blind study in two parallel groups with respect to nifedipine (placebo or 5 mg nifedipine). Ocular hemodynamics in the 12 healthy subjects participating in the study was assessed by laser interferometric measurement of fundus pulsation amplitude (FPA) in the optic disc and two-dimensional scanning laser Doppler flowmetry in the optic disc.

ET-1 caused a dose-dependent decrease in FPA and flow. With a dose of 4 ng/kg/min a decrease of -18% +/- 5% (p < 0.001) and -17% +/- 5% (p = 0.023) on FPA and flow, respectively, were observed. This effect was completely reversed by nifedipine compared with placebo (FPA, p < 0.001; flow, p = 0.011). However, nifedipine did not affect ocular hemodynamics after placebo infusion.

These results show that nifedipine does not increase optic nerve head blood flow during baseline conditions but reverses ET-1-induced constriction in ocular vasculature at doses that do not affect systemic hemodynamics. This supports the close relation of the therapeutic effect of calcium channel blockers in patients with normal tension glaucoma to the endothelin system. Moreover, the present study provides a strong rationale for a study of low dose nifedipine as a supplementary medication in glaucoma patients.