Intravenous Administration of Diphenhydramine Reduces Histamine-Induced Vasodilator Effects in the Retina and Choroid

Abstract

Intravenous administration of histamine causes an increase in choroidal blood flow (ChBF) and retinal vessel diameters in healthy subjects. The receptor mediating this response has not yet been identified. The present study was undertaken to clarify whether H1 receptor blockade with diphenhydramine affects the hemodynamic response of histamine in the choroid and the retina. A randomized, double-masked, placebo-controlled, two-way crossover study was performed in 18 healthy, male, nonsmoking subjects. Histamine (0.32 microg/kg per minute over 30 minutes) was infused intravenously in the absence (NaCl as placebo) or presence of the H1 blocker diphenhydramine (1.0 mg/min over 50 minutes). Ocular hemodynamic parameters, blood pressure, and intraocular pressure were measured before drug administration, after infusion of diphenhydramine or placebo, and after co-infusion of histamine. Subfoveal ChBF and fundus pulsation amplitude (FPA) were measured with laser Doppler flowmetry and laser interferometry, respectively. Retinal arterial and venous diameters were measured with a retinal vessel analyzer. Retinal blood velocity was assessed with bidirectional laser Doppler velocimetry. Administration of histamine caused a decrease in mean arterial pressure by -4% +/- 9% (ANOVA P = 0.01). This effect was blunted by coadministration of diphenhydramine (ANOVA, P = 0.04). Histamine significantly increased FPA and subfoveal ChBF. Coadministration of diphenhydramine significantly reduced this effect (ANOVA; FPA P = 0.001, ChBF P = 0.049). Histamine significantly increased retinal arterial diameter by +3.5% +/- 4.5% and retinal venous diameter by +3.7% +/- 2.8%. Again, coadministration of diphenhydramine significantly reduced the vasodilative effect to +0.3% +/- 5.5% in retinal arteries (ANOVA, P = 0.00006) and to +0.9% +/- 2.5% in retinal veins (ANOVA, P = 0.004). The present data confirm that histamine increases ChBF and retinal vessel diameters in healthy subjects. Administration of the H1 receptor blocker diphenhydramine significantly reduced histamine-induced changes in ocular perfusion parameters. These results strongly indicate that in the retina and choroid, H1 receptors are involved in the histamine-mediated hemodynamic effects in vivo.