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Klin Monbl Augenheilkd 2001; 218(5): 351-353
DOI: 10.1055/s-2001-15898
EXPERIMENTELLE STUDIE

Georg Thieme Verlag Stuttgart · New York

Topical ocular instillation of nitric oxide synthase inhibitors and intraocular pressure in rabbits[1]

Topische Anwendung von Stickstoffmonoxydsynthetase-Inhibitoren zeigt keinen Einfluss auf den intraokularen Druck beim KaninchenJohannes  C. Fleischhauer1 , Rong Liu1 , Pierre-Paul Elena2 , Josef Flammer1 , Ivan  O. Haefliger1
  • 1 Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic Basel, Mittlere Strasse 91, PO Box, CH-4012 Basel (Dir.: Josef Flammer)
  • 2 Iris Pharma, La Gaude, France
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Publication Date:
31 December 2001 (online)

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Topische Anwendung von Stickstoffmonoxydsynthetase-Inhibitoren zeigt keinen Einfluss auf den intraokularen Druck beim Kaninchen

Hintergrund Beim Kaninchen führt die intravenöse Anwendung des kompetitiven Stickstoffmonoxydsynthetase (NOS)-Hemmers NG-nitro-L-arginine methyl esther (L-NAME) zu einer schnellen Senkung des Intraokulardruckes (IOD). Vorliegende Studie wurde durchgeführt, um den Effekt verschiedener topisch applizierter NOS-Hemmer auf eine wasserinduzierte IOD-Steigerung zu ermitteln.

Methodik 40 männliche Albino-New-Zealand-Kaninchen (2,0 - 2,5 kg) erhielten nach dem Zufallsprinzip 3-mal in das rechte Auge 50 μl entweder 0,9 % NaCl, 0,5 % timolol maleate, 0,5 % 7-nitroindazole (7-NI; neuronaler NOS-Inhibitor), 0,5 % L-NAME, oder 0,5 % 2-amino-5,6-dihydro-6-methyl-1,3,-thiazine (AMT; Selectiver Hemmer der induzierbaren NOS) instilliert. Der Augendruck wurde vor der Instillation der Medikamente (baseline), direkt danach (0), sowie 15, 30, 60, 90 und 120 Minuten nach oraler Gabe destillierten Wassers (60 ml/kg KG) gemessen (TonoPen™). Zur Datenanalyse wurde die Fläche unter der Kurve (AUC: IOP versus Zeit) mittels ANOVA zwischen den verschiedenen Gruppen verglichen.

Resultate Am rechten Auge betrugen die AUC-Werte 527 ± 284 für NaCl, 255 ± 178 für Timolol, 466 ± 242 für 7-NI, 604 ± 195 für L-NAME und 394 ± 202 für AMT. Die AUC-Werte waren nur in der Timolol-Gruppe signifikant (p < 0,05) vermindert. In den linken Augen konnten keine signifikanten Unterschiede (p > 0,05) in der AUC zwischen den verschiedenen Gruppen beobachtet werden.

Schlussfolgerung Unter den vorliegenden Versuchsbedingungen konnte kein signifikanter Einfluss von NOS-Hemmern (7-NI, L-NAME, AMT) auf eine durch eine perorale Wassergabe bedingte Augendruckerhöhung festgestellt werden.

Abstract

Purpose It has been reported that intravenous injection of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl esther (L-NAME) causes a rapid decrease of intraocular pressure (IOP) in rabbits. This study investigates the effect of topical ocular application of different NOS inhibitors on a raise of IOP induced by an acute water intake (rabbit water loading model).

Methods Forty New Zealand (albino) male rabbits received randomly (within thirty minutes) in their right eye three 50 μl installations of either 0.9 % NaCl, 0.5 % timolol maleate (β-adrenoreceptor antagonist), 0.5 % 7-nitroindazole (7-NI; NOS inhibitor), 0.5 % L-NAME, or 0.5 % 2-amino-5,6-dihydro-6-methyl-1,3,-thiazine (AMT; NOS inhibitor) before an oral water gavage (60 ml/kg). IOP was measured (TonoPen™) before and after topical instillation (time 0), and then 15, 30, 60, 90, and 120 minutes after water intake.

Results In right eyes, the area under the curve (AUC) of the IOP difference versus time (arbitrary units) was 527 ± 284 for NaCl, 255 ± 178 for timolol, 466 ± 242 for 7-NI, 604 ± 195 for L-NAME, and 394 ± 202 for AMT. Values of AUC were only significantly lower (p < 0.05) in the timolol-treated group. In left eyes, no significant difference (p > 0.05) could be observed in values of AUC between groups.

Conclusions Under the present experimental conditions (including concentration and bioavailability of the drugs used), topical application of the NOS inhibitors 7-NI, L-NAME, and AMT does not prevent an IOP increase induced by water intake in rabbits.

Schlüsselwörter

Kammerwasserproduktion - Exzitotoxizität - Glutamat - Glaukom - Neuroprotektion - Stickstoffmonoxid

Key words

Aqueous humour production - excitotoxicity - glutamate - glaucoma - neuroprotection - nitric oxide

1 1 This work was supported by Transphyto SA (Clermont-Ferrand, France) the Swiss National Science Foundation grants #32-52783.97 and #32-061495.00 (Bern, Switzerland), and the Roche Research Foundation (Basel, Switzerland).

References

1 1 This work was supported by Transphyto SA (Clermont-Ferrand, France) the Swiss National Science Foundation grants #32-52783.97 and #32-061495.00 (Bern, Switzerland), and the Roche Research Foundation (Basel, Switzerland).

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