Sildenafil stimulates aqueous humor turnover in rabbits

- Sildenafil ingestion increased aqueous humor (AH) production in live rabbits.
- AH production was measured with a scanning ocular fluorophotometer.
- AH production increased by 36% after the rabbits ingested sildenafil.
- T1/2 for AH replacement was about 60 min under control conditions.
- T1/2 for AH replacement was about 44 min after sildenafil ingestion.

Sildenafil citrate increases ocular blood flow and accelerates the rate of anterior chamber refilling after paracentesis. The latter effect could have resulted from a reduction in outflow facility or from an increase in aqueous humor (AH) production. In this study, we used scanning ocular fluorophotometry to examine the effects of sildenafil on AH turnover, and thus, AH production in eyes of live normal rabbits. For this, the rate of aqueous humor flow (AHF) was quantified with a commercially available fluorophotometer that measured the rate of fluorescein clearance from the anterior segment, which predominantly occurs via the trabecular meshwork. After ≈2 h of control scans to determine the baseline rate of AHF, the rabbits were fed 33 mg of sildenafil and allowed ≈45 min for the drug to enter the systemic circulation. Thereafter, fluorescence scans were retaken for an additional 90-120 min. Sildenafil ingestion increased AHF by about 36%, from 2.31 μL/min to 3.14 μL/min (P < 0.001, as two-tailed paired data, n = 20 eyes). This observation indicates that sildenafil citrate, which is a phosphodiesterase type-5 inhibitor currently marketed as a vasodilator (e.g., Viagra, Revatio), stimulates AHF in rabbits. Our results seem consistent with reports indicating that the drug dilates intraocular arteries and augments intraocular vascular flow. These physiological responses to the agent apparently led to increased fluid entry into the anterior chamber. As such, the drug might have utility in patients with ocular hypotony resulting from insufficient AH formation.