Pharmacodynamics of beta-blocker modulation of aqueous humor production.
A conscious rabbit model with microdialysis sampling of endogenous aqueous humor ascorbate was developed in order to assess the pharmacodynamics of beta-blocker modulation of aqueous humor production. CMA/20 microdialysis probes were implanted in the anterior chamber of each eye of rabbits (n = 6). After a 2 week recovery period, an i.v. bolus of 14C-ascorbate (20 microCi) was administered. Blood samples and aqueous humor microdialysis probe effluent were collected and analysed for endogenous and 14C-ascorbate to estimate the basal rate of ascorbate blood to aqueous humor secretion (Ro). After a 1 hr washout, each rabbit received a series of three doses of 3H-propranolol (750-3000 microg, 16.5 microCi mg(-1)) every 60 min into the lower cul-de-sac of each eye. Probe effluent was analysed for endogenous ascorbate and 3H-propranolol; ascorbate and propranolol in the iris/ciliary body, vitreous and aqueous was determined at the end of the experiment. Nonlinear least-squares regression analysis of the concentration-time profiles for aqueous humor ascorbate was performed to estimate the change in aqueous humor flow. The average basal aqueous humor ascorbate secretion rate was approximately 48/microg hr(-1). Propranolol (1500 microg) produced significant increases in aqueous humor ascorbate, this observation is consistent with a reduction in aqueous humor production (approximately 47%). Analysis of intraocular tissue ascorbate indicated that propranolol inhibited ascorbate secretion at the 3000 microg dose, the highest dose examined in this study; this inhibition was not observed at the 750 microg or 1500 microg doses. Changes in aqueous humor production precipitated by the administration of beta-adrenergic antagonists can be estimated by measuring changes in aqueous humor ascorbate concentrations in the conscious rabbit. Microdialysis sampling of aqueous humor for endogenous ascorbate provides a relevant analytic tool to estimate modulatory effects of anti-glaucoma drugs on aqueous humor production.
Rittenhouse
K D
KD
Preclinical Sciences, Bausch & Lomb Pharmaceuticals, Tampa, FL 33637, USA.
Pollack
G M
GM
D000086:Acetazolamide / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D019540:Area Under Curve; D002250:Carbon Radioisotopes / Q000097:blood; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002924:Ciliary Body / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D007498:Iris / Q000737:chemistry; D016018:Least-Squares Analysis; D017551:Microdialysis; D011433:Propranolol / Q000494:pharmacology*; D011817:Rabbits; D012680:Sensitivity and Specificity; D014316:Tritium; D014822:Vitreous Body / Q000737:chemistry
D000319:Adrenergic beta-Antagonists; D002250:Carbon Radioisotopes; D002257:Carbonic Anhydrase Inhibitors; D014316:Tritium; D011433:Propranolol; D000086:Acetazolamide