Effect of Systemic Nitric Oxide Synthase Inhibition on Optic Disc Oxygen Partial Pressure in Normoxia and in Hypercapnia

¹ Department of Ophthalmology, University Hospital of Geneva, Geneva, Switzerland
² Jules Gonin Eye Hospital, University of Lausanne, Lausanne, Switzerland
³ Department of Ophthalmology, University Hospital of Geneva, Rue Alcide-Jentzer 22, Geneva, 1211 GE 14, Switzerland

^* To whom correspondence should be addressed. E-mail: constantin.pournaras{at}hcuge.ch.

	Abstract

PURPOSE. To investigate the effect of systemic nitric oxide synthase (NOS) inhibition on optic disc oxygen partial pressure (PO₂) in normoxia and hypercapnia. METHODS. We measured intervascular optic disc PO₂ in 12 anesthetized minipigs using oxygen-sensitive microelectrodes placed <50 µm from the optic disc. PO₂ was measured continuously during 10 minutes under normoxia, hyperoxia (100% O₂), carbogen breathing (95% O₂, 5% CO₂), and hypercapnia (increased inhaled CO₂). Measurements were repeated after intravenous injection of N-nitro-L-arginine methyl ester (L-NAME) 100 mg/kg. Intravenous L-arginine 100 mg/kg was subsequently given to three animals. RESULTS. Before L-NAME injection, we observed an increase in optic disc PO₂ during hypercapnia (PO₂ = 3.2 ± 1.7 mm Hg; 18%; P = 0.001) and carbogen breathing (PO₂ = 12.8 ± 5.1 mm Hg; 69%; P < 0.001). Optic disc PO₂ in normoxia remained stable during 30 minutes following L-NAME injection (4% decrease from baseline; P > 0.1) despite a 21% increase of mean arterial pressure. Optic disc PO₂ increase under hypercapnia was blunted following L-NAME injection (PO₂ = 0.6 ± 1.1 mm Hg; 3%; P > 0.1), and this effect was reversible by L-arginine. Moreover, L-NAME reduced the response to carbogen by 29% (PO₂ = 9.1 ± 4.4 mm Hg; 49%; P = 0.01 versus before L-NAME). The response to hyperoxia was not affected. CONCLUSIONS. While systemic NOS inhibition did not affect optic disc PO₂ in normoxia, a blunting effect was noted on CO₂-induced optic disc PO₂ increase. Nitric oxide appears to mediate hypercapnic optic disc PO₂ increase.

Key Words: optic disc, nitric oxide, oxygen partial pressure, carbon dioxide, L-NAME, hypercapnia