Adrenergic mechanism in circadian elevation of intraocular pressure in rabbits.
Stimulation of the ocular sympathetic nerves is essential for the circadian elevation of intraocular pressure (IOP) in rabbits. Adrenergic mechanisms that participate in this elevation of IOP around the onset of darkness were investigated using selective adrenergic agents. Unilateral topical administration of 0.0001-0.1% prazosin, an alpha-1-adrenergic antagonist, at the onset of darkness caused a dose-dependent reduction of IOP elevation. After treatment with 0.1% prazosin, the concentration of norepinephrine (NE) in aqueous humor was not changed, but the aqueous humor protein concentration was reduced. The increase of aqueous flow, determined by fluorophotometry, after the onset of darkness was not affected by 0.1% prazosin treatment. Treatment of rauwolscine, an alpha-2-adrenergic antagonist, or timolol, a beta-adrenergic antagonist, was ineffective in reducing the circadian elevation of IOP. Apraclonidine, an alpha-2-adrenergic agonist, with concentrations of 0.0001-1% caused a dose-dependent reduction of IOP elevation. Treatment with 1% apraclonidine caused a 70% reduction of aqueous humor NE, a significant attenuation of the increase of aqueous flow, and no change of aqueous humor protein concentration. These results suggest that both an increase of aqueous outflow resistance (by alpha-1-adrenergic receptors) and an increase of aqueous flow (not exclusively by beta-adrenergic receptors) contribute to the circadian elevation of IOP. Prejunctional alpha-2-adrenergic receptors may serve as an autoregulating mechanism to limit the excess release of NE and hypertensive spike in IOP.
Eye Research Institute of Retina Foundation, Boston, MA 02114.
J H
JH
Liu
A C
AC
Dacus
S P
SP
Bartels
D000287:Administration, Topical; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000378:metabolism; D015590:Fluorophotometry; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D005136:Eye Proteins; D009638:Norepinephrine