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Effect of systemic nitric oxide synthase inhibition on optic disc oxygen partial pressure in normoxia and in hypercapnia

Pournaras, Jean-Antoine C.
Stangos, Alexandros N.
Published in Investigative Ophthalmology and Visual Science, IOVS. 2009, vol. 50, no. 1, p. 378-84
Abstract PURPOSE: To investigate the effect of systemic nitric oxide synthase (NOS) inhibition on optic disc oxygen partial pressure (PO(2)) in normoxia and hypercapnia. METHODS: Intervascular optic disc PO(2) was measured in 12 anesthetized minipigs by using oxygen-sensitive microelectrodes placed <50 microm from the optic disc. PO(2) was measured continuously during 10 minutes under normoxia, hyperoxia (100% O(2)), carbogen breathing (95% O(2), 5% CO(2)), and hypercapnia (increased inhaled CO(2)). Measurements were repeated after intravenous injection of N(omega)-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, an increase was observed in optic disc PO(2) during hypercapnia (DeltaPO(2) = 3.2 +/- 1.7 mm Hg; 18%; P = 0.001) and carbogen breathing (DeltaPO(2) = 12.8 +/- 5.1 mm Hg; 69%; P < 0.001). Optic disc PO(2) in normoxia remained stable for 30 minutes after L-NAME injection (4% decrease from baseline; P > 0.1), despite a 21% increase of mean arterial pressure. Optic disc PO(2) increase under hypercapnia was blunted after L-NAME injection (DeltaPO(2) = 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% (DeltaPO(2) = 9.1 +/- 4.4 mm Hg; 49%; P = 0.01 versus before L-NAME). The response to hyperoxia was not affected. CONCLUSIONS: Whereas systemic NOS inhibition did not affect optic disc PO(2) in normoxia, a blunting effect was noted on the CO(2)-induced optic disc PO(2) increase. Nitric oxide appears to mediate the hypercapnic optic disc PO(2) increase.
Keywords AnimalsArginine/administration & dosageBlood PressureCarbon Dioxide/administration & dosageEnzyme Inhibitors/administration & dosageHypercapnia/bloodHyperoxia/bloodInjections, IntravenousIon-Selective ElectrodesMicroelectrodesNG-Nitroarginine Methyl Ester/administration & dosageNitric Oxide Synthase Type II/antagonists & inhibitorsOptic Disk/blood supplyOxygen/administration & dosage/bloodOxygen Consumption/physiologyPartial PressureSwineSwine, Miniature
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Other version: http://www.iovs.org/cgi/content/full/50/1/378
PMID: 18676634
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