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O. A. Candia, R. Gerometta; Effects of Sildenafil and Tadalafil on Intraocular Pressure in Sheep; Implications on Aqueous Humor Dynamics. Invest. Ophthalmol. Vis. Sci. 2010;51(13):159.
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To determine the effects of vasodilators on intraocular pressure (IOP) and protein content of sheep aqueous humor (AH), because 1) the vasodilators might increase fluid leakage from the fenestrated capillaries of the ciliary body to the extracellular tissue and directly to the anterior chamber (AC) via the iris, and 2) some patients (older than 70) treated with sildenafil have exhibited elevated IOP.
Experiments were done on domestic sheep residing on a ranch in Argentina. These are docile, easy to handle and compliant animals. They readily swallowed tablets of sildenafil (50 and 100 mg) and tadalafil (20 mg). IOP was monitored by Perkins applanation tonometry in 21 normal sheep orally administered these drugs. In addition, paracentesis was performed on 6 sheep to quantify changes in AH protein levels with the Pierce protein assay.
Ingestion of both sildenafil and tadalafil increased sheep IOP from normal levels of ≈ 9-11 mmHg within 1 hr. The IOP elevation was ≈ 1.6 fold with both doses of sildenafil. IOP returned to control values within 4 hrs. With the longer-lasting vasodilator tadalafil, IOP remained 1.6 to 1.9-fold higher than normal for at least 48 hrs and returned to control levels within 4 days. The AH protein content was 60% higher after administering 100 mg sildenafil. No other drugs or doses were tested on this parameter.
These data are consistent with a vasodilator-evoked increase in plasma-like fluid into the AC, which likely accounts for the IOP elevation. As such, the results 1) support the existence of a parallel pathway directly from the ciliary stroma to the AC, and 2) may be relevant to the management of IOP in senior patients treated with these compounds for vascular diseases, especially those patients with glaucoma. Sheep may be an ideal model for further studies.
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