Metabolic Regulation of the Hypercapnia–Associated Vasodilation of the Optic Nerve Head Vessels

Abstract

Abstract: : Purpose: To search for mediators of the hypercapnia–associated vasodilation of the optic nerve head vessels. Prostaglandins and nitric oxide (NO) have been shown to mediate the hypercapnia–associated vasodilation in the retina. Moreover, PO₂ measurements are closely associated to local tissue blood flow. Methods: We measured the PO₂ at intervascular areas of the optic disc in 17 anaesthetized miniature pigs using oxygen–sensitive microelectrodes placed at less than 50 microns from the optic disc. PO₂ was measured continuously during 10 minutes under systemic normoxia, systemic hyperoxia (breathing of 100% O₂), carbogen breathing (95% O₂, 5% CO₂), and hypercapnia (40% increase in inhaled CO₂). Similar measurements were also done after intravenous administration of the prostaglandin inhibitor indomethacin (6 animals) or the NO synthase inhibitor L–NAME (6 animals). Results: Before the injections, we observed a slight increase in the optic disc PO₂ during hypercapnia (ΔPO₂=1.9±1.7 mmHg) as well as during hyperoxia (ΔPO₂=3.4±1.6 mmHg), but a much more important increase during carbogen breathing (ΔPO₂=12.3±5.2 mmHg). After the injection of indomethacin, the increase in the optic disc PO₂ was similar during hyperoxia (ΔPO₂=5.6±2.2 mmHg) or carbogen breathing (ΔPO₂=5.8±3.2 mmHg). Moreover, the variation of the optic disc PO₂ was minimal in hypercapnia after the injection of either indomethacin (ΔPO₂=0.5±1.9 mmHg) or L–NAME (ΔPO₂=0.7±1.3 mmHg). Conclusions: Indomethacin fully inhibits the vasodilating effect of increased systemic PaCO₂ on the optic disc vessels, leading to a similar moderate increase in the optic disc PO₂ during carbogen breathing as in hyperoxia. In addition, indomethacin or L–NAME inhibits the increase in the optic disc PO₂ seen during hypercapnia. Those results indicate that prostaglandins and, to a lesser extent, NO are mediators of the hypercapnia–associated vasodilation of the optic disc vessels. CO₂–induced optic nerve head vasodilation is probably due to a combined effect of prostaglandins and NO.

Keywords: nitric oxide • optic disc • pharmacology