Evaluation of nitric oxide synthesis in the optic nerve head in vivo using microdialysis and high-performance liquid chromatography and its interaction with endothelin-1.
OBJECTIVE
To investigate the relationship between nitric oxide synthesis and endothelin-1 (ET-1) in the optic nerve head in vivo.


METHODS
A concentric microdialysis probe was inserted into the optic nerve head of a rabbit and was perfused with Ringer's solution at a constant flow rate of 2 microl/min. The perfused dialysates were collected every 10 min, and levels of nitrite and nitrate in the 10-min dialysate samples were measured after intravitreal injection of ET-1 (100 pmol) using high-performance liquid chromatography based on the Griess method.


RESULTS
Basal levels of nitrite and nitrate in the 10-min dialysate were 0.08 +/- 0.01 and 3.95 +/- 0.50 microM, respectively. We confirmed that these levels were reduced by intravenous L-NAME and restored by L-arginine. Intravitreal ET-1 significantly elevated the levels of nitrate to 189% of baseline 10 min after ET-1 application, which was inhibited by pretreatment of intravenous L-NAME (50 mg/kg).


CONCLUSIONS
These results indicate that production of nitric oxide is closely connected with the ET-1 signaling pathway.
Okuno
Takashi
T
Department of Ophthalmology, Osaka Medical College, Osaka, Japan.
Oku
Hidehiro
H
Sugiyama
Tetsuya
T
Goto
Wakana
W
Ikeda
Tsunehiko
T
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004347:Drug Interactions; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects; D017551:Microdialysis / Q000379:methods; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester