Role of Endothelin- and Nitric Oxide-system in the Regulation of Optic Nerve Head Blood Flow During Changes in Ocular Perfusion Pressure

Medical University of Vienna

Status and phase

Withdrawn

Phase 2

Conditions

Optic Disk

Regional Blood Flow

Ocular Physiology

Treatments

Drug: NG-monomethyl-L-arginine (L-NMMA)

Device: HP-CMS patient monitor

Drug: Physiologic saline solution (placebo control)

Device: Laser Doppler flowmetry

Device: Goldmann applanation tonometer

Drug: Endothelin-1 (ET-1)

Procedure: Suction cup method

Study type

Interventional

Funder types

Other

Identifiers

NCT00406731

OPHT-080206

Details and patient eligibility

About

Autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. The existence of an effective autoregulation in the optic nerve circulation has been shown in animals and humans. The exact mechanism behind this autoregulation is still unknown. The motive for the investigation of optic nerve head (ONH) blood flow autoregulation is to enhance the understanding of pathologic eye conditions associated with ocular vascular disorders. To clarify the regulatory mechanisms of ONH microcirculation is of critical importance to understand the pathophysiology of glaucoma because there is evidence that glaucoma is associated with optic nerve head ischemia. Several studies indicate that a disturbed autoregulation might contribute to glaucomatous optic neuropathy. Previous findings suggest endothelial dysfunction in glaucomatous optic neuropathy, in particular alterations in endothelin- and nitric oxide- system, which both play an important role in local regulation of vascular tone.

In the present study, changes in ocular perfusion pressure will be performed during administration of drugs, which may potentially alter the pressure-flow relationship. These drugs include endothelin-1 and the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA).

Sex

Male

Ages

18 to 35 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Men aged between 18 and 35 years, nonsmokers
Body mass index between 15th and 85th percentile (Must et al. 1991)
Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant
Normal ophthalmic findings, ametropy < 1 Dpt

Exclusion criteria

Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study
Treatment in the previous 3 weeks with any drug
Symptoms of a clinically relevant illness in the 3 weeks before the first study day
History of hypersensitivity to the trial drug or to drugs with a similar chemical structure
History or presence of systemic or pulmonary hypertension, or other cardiac or pulmonary diseases
History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with, distribution, metabolism or excretion of study drugs
Blood donation during the previous 3 weeks