Effect of systemic nitric oxide synthase inhibition on optic disc oxygen partial pressure in normoxia and in hypercapnia.
OBJECTIVE
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.
Petropoulos
Ioannis K
IK
Laboratory of Ocular Vascular Diseases, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Pournaras
Jean-Antoine C
JA
Stangos
Alexandros N
AN
Pournaras
Constantin J
CJ
D000818:Animals; D001120:Arginine / Q000008:administration & dosage; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006935:Hypercapnia / Q000097:blood*; D018496:Hyperoxia / Q000097:blood; D007275:Injections, Intravenous; D017736:Ion-Selective Electrodes; D008839:Microelectrodes; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D009898:Optic Disk / Q000098:blood supply*; D010100:Oxygen / Q000008:administration & dosage / Q000097:blood*; D010101:Oxygen Consumption / Q000502:physiology; D010313:Partial Pressure; D013552:Swine; D013556:Swine, Miniature
D004791:Enzyme Inhibitors; D002245:Carbon Dioxide; C011700:carbogen; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester