Intraocular pressure increases with fenoldopam, but not nitroprusside, in hypertensive humans

Abstract

Fenoldopam mesylate stimulates adenyl cydase in porcine ocular trabecular meshwork and raises intraocular pressure in humans. To clarify whether this results from direct activation of the dopamine‐1 receptor or indirectly from baroreflex sympathetic stimulation after blood pressure reduction, intraocular pressure was measured in 14 patients with accelerated/malignant hypertension, randomized between intravenous fenoldopam or sodium nitroprusside. Intraocular pressure was measured with a Perkins tonometer, before and at the twentieth minute of each dose increment. In seven patients with a mean blood pressure of 232/131 mm Hg treated with fenoldopam, intraocular pressure increased in a dose‐dependent fashion, from 16 ± 1 to 20 ± 2 mm Hg (p < 0.005). In contrast, seven patients with a mean blood pressure of 225/134 mm Hg treated with sodium nitroprusside exhibited no change in intraocular pressure (15 ± 1 versus 14 ± 1 mm Hg) despite similar blood pressure reduction. Increases in heart rate were not significantly different. Rates of urinary excretion of norepinephrine plus epinephrine increased significantly relative to baseline (p < 0.05) but were not different between groups. These data suggest that the increase in intraocular pressure with fenoldopam results from specific activation of the dopamine‐1 receptor and is not caused by baroreflex sympathetic stimulation. Because dopamine‐1 receptors may modulate intraocular pressure, dopamine‐1 receptor blockers might be useful therapy for glaucoma. Clinical Pharmacology and Therapeutics (1991) 49, 285–293; doi:

Comparison of non‐invasive methods for the assessment of haemodynamic drug effects in healthy male and female volunteers: sex differences in cardiovascular responsiveness.

“…While we have not measured IOP in our study during infusion periods, the expected changes in IOP are several orders of magnitude lower than changes in systolic and diastolic blood pressure of choroid vasculature [19,22]. Regional ocular blood flow can be influenced by both a-and f-adrenoceptor mimetic drugs [23], but this vascular effect was not detected by laser interferometry.…”

“…We evaluated the potential of non-invasive measurements of ocular fundus pulsations by laser interferometry for the characterisation of druginduced haemodynamic effects. Previous studies have only addressed intraocular pressure changes by tonometric methods [18,19]. Figure 2).…”

Fenoldopam — A Selective Peripheral Dopamine-Receptor Agonist for the Treatment of Severe Hypertension

“…32 In subsequent studies in patients with accelerated or malignant hypertension, those who were given an intravenous infusion of fenoldopam had an increase in intraocular pressure, whereas there was no change in the intraocular pressure in the patients given nitroprusside who had similar reductions in blood pressure. 75 The increase in intraocular pressure induced by fenoldopam has been attributed, at least in part, to diminished drainage of aqueous humor. 76 Fenoldopam also increases the intraocular pressure in patients with ocular hypertension, and the increase may be more marked than in patients with normal intraocular pressure.…”

Fenoldopam, A Selective Dopamine-1 Receptor Agonist, Raises Intraocular Pressure in Males with Normal Intraocular Pressure

“…A second study evaluated fourteen hypertensive subjects admitted to a critical care center for acute reduction of blood pressure (6). Patients were randomized to receive escalating doses of either intravenous fenoldopam or nitroprusside titrated to lower diastolic blood pressure to 100 to 110 mmHg.…”

“…Intravenous infusion of fenoldopam (0.5 Mg/kg/min) elevated IOP by 22% in normal human volunteers (5). In patients with severe systemic hypertension, either fenoldopam or nitroprusside lowered blood pressure, but only fenoldopam raised IOP; this indicated that fenoldopam's IOP response occurs independently of changes in systemic blood pressure (6).…”