Topically Applied Hydralazine: Effects on Systemic Cardiovascular Parameters, Blood-Aqueous Barrier, and Aqueous Humor Dynamics in Normotensive Humans

Abstract

Local application of hydralazine has been found to alter intraocular pressure in animal eyes. This study was undertaken to determine, in normotensive humans, the effects of topically-applied hydralazine on systemic cardiovascular parameters, blood-aqueous barrier, and aqueous humor flow. Two different concentrations of hydralazine were used: 0.03%, and 0.1%. Twenty healthy normotensive subjects were studied. Blood pressure, pulse rate, and intraocular pressure were measured every hour for six hours after hydralazine or placebo was instilled into the conjunctival sac in a double-masked, randomized fashion. With either hydralazine dose, there was no significant change in systemic blood pressure or pulse. In addition, spectrophotometrically-measured polarization of fluorescence and flare failed to show any significant breakdown of the blood-aqueous barrier. In most individuals, application of hydralazine was followed by a brief, mild to moderate, conjunctival hyperemic response. Compared to placebo at the same time of day, a small increase in intraocular pressure was observed with 0.03% hydralazine (p < .05). At 0.1%, this increase tended to be less. There was no statistically significant difference in aqueous humor flow between hydralazine-treated and placebo-treated eyes at the lower concentration (3.20 +/- 0.63 vs. 3.05 +/- 0.61 microL/min (mean +/- S.D.) or at the higher concentration (3.37 +/- 0.53 vs. 3.28 +/- 0.60 microL/min) of hydralazine. These results suggest that acute topical application of 0.1% hydralazine to the eyes of normal humans does not cause clinically significant cardiovascular effects or significant ocular toxicity.

Morphine-Induced Reduction of Intraocular Pressure and Pupil Diameter: Role of Nitric Oxide

“…Some studies have shown that both topical and intraocular administration of NO donors reduced IOP [30][31][32], while others reported that topical NO donors increased the IOP without affecting aqueous humor formation [33] or outfl ow facility [34] . Yet, other studies have shown that NO donors have no effect on the IOP in rabbits [35] or humans [36] .…”

Effects of Nitric Oxide Synthase Inhibition on Ciliary Blood Flow, Aqueous Production and Intraocular Pressure

“…Some authors report that topical and intraocular NO donors decrease IOP (Nathanson and McKee, 1995;Behar-Cohen et al, 1996), possibly by increasing conventional out¯ow facility (Schuman, Erikson and Nathanson, 1994). By contrast, other studies ®nd that topical NO donors increase IOP without affecting aqueous production (Larson et al, 1995) or tonographic out¯ow facility (Krupin et al, 1977). Interestingly, there are also reports that systemic NOS inhibition has no effect on IOP in conscious humans (Kiss et al, 1999) and rabbits (Taniguchi et al, 1998).…”

Concentration-related effects of nitric oxide and endothelin-1 on human trabecular meshwork cell contractility

“…Administration of NO donors or overexpression of NO producing enzyme endothelial nitric oxide synthase (eNOS) results in increased outflow facility and/or decreased IOP in a number of animals including humans (Dismuke et al, 2008; Heyne et al, 2013; Larsson et al, 1995; Nathanson, 1992; Stamer et al, 2011). Nitric oxide synthase has also been detected in the tissues of the outflow pathway (Nathanson and McKee, 1995) and inhibition of this enzyme results in decreased outflow (Schneemann et al, 2002).…”