Pharmacodynamics of beta-blocker modulation of aqueous humor production

Kay D. Rittenhouse; Gary M. Pollack

doi:10.1006/exer.1999.0805

Pharmacodynamics of beta-blocker modulation of aqueous humor production

Kay D. Rittenhouse
, Gary M. Pollack

School of Pharmacy and Pharmaceutical Sciences

Bausch & Lomb Incorporated

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

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 μCi) 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 μg, 16.5 μCi 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 ~ 48 μg hr^-1. Propranolol (1500 μg) produced significant increases in aqueous humor ascorbate, this observation is consistent with a reduction in aqueous humor production (~ 47%). Analysis of intraocular tissue ascorbate indicated that propranolol inhibited ascorbate secretion at the 3000 μg dose, the highest dose examined in this study: this inhibition was not observed at the 750 μg or 1500 μg 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. (C) 2000 Academic Press.

Original language	English
Pages (from-to)	429-439
Number of pages	11
Journal	Experimental Eye Research
Volume	70
Issue number	4
DOIs	https://doi.org/10.1006/exer.1999.0805
State	Published - 2000

Keywords

Aqueous humor turnover
Ascorbate
Beta-adrenergic antagonist
Microdialysis
Pharmacodynamics
Rabbit

Access to Document

10.1006/exer.1999.0805

Cite this

@article{25e7eb91e6154c4e8984d2fac8ed705f,

title = "Pharmacodynamics of beta-blocker modulation of aqueous humor production",

abstract = "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 μCi) 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 μg, 16.5 μCi 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 \textasciitilde{} 48 μg hr-1. Propranolol (1500 μg) produced significant increases in aqueous humor ascorbate, this observation is consistent with a reduction in aqueous humor production (\textasciitilde{} 47\%). Analysis of intraocular tissue ascorbate indicated that propranolol inhibited ascorbate secretion at the 3000 μg dose, the highest dose examined in this study: this inhibition was not observed at the 750 μg or 1500 μg 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. (C) 2000 Academic Press.",

keywords = "Aqueous humor turnover, Ascorbate, Beta-adrenergic antagonist, Microdialysis, Pharmacodynamics, Rabbit",

author = "Rittenhouse, \{Kay D.\} and Pollack, \{Gary M.\}",

year = "2000",

doi = "10.1006/exer.1999.0805",

language = "English",

volume = "70",

pages = "429--439",

journal = "Experimental Eye Research",

issn = "0014-4835",

publisher = "Academic Press",

number = "4",

}

TY - JOUR

T1 - Pharmacodynamics of beta-blocker modulation of aqueous humor production

AU - Rittenhouse, Kay D.

AU - Pollack, Gary M.

PY - 2000

Y1 - 2000

N2 - 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 μCi) 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 μg, 16.5 μCi 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 ~ 48 μg hr-1. Propranolol (1500 μg) produced significant increases in aqueous humor ascorbate, this observation is consistent with a reduction in aqueous humor production (~ 47%). Analysis of intraocular tissue ascorbate indicated that propranolol inhibited ascorbate secretion at the 3000 μg dose, the highest dose examined in this study: this inhibition was not observed at the 750 μg or 1500 μg 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. (C) 2000 Academic Press.

AB - 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 μCi) 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 μg, 16.5 μCi 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 ~ 48 μg hr-1. Propranolol (1500 μg) produced significant increases in aqueous humor ascorbate, this observation is consistent with a reduction in aqueous humor production (~ 47%). Analysis of intraocular tissue ascorbate indicated that propranolol inhibited ascorbate secretion at the 3000 μg dose, the highest dose examined in this study: this inhibition was not observed at the 750 μg or 1500 μg 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. (C) 2000 Academic Press.

KW - Aqueous humor turnover

KW - Ascorbate

KW - Beta-adrenergic antagonist

KW - Microdialysis

KW - Pharmacodynamics

KW - Rabbit

UR - https://www.scopus.com/pages/publications/0033836933

U2 - 10.1006/exer.1999.0805

DO - 10.1006/exer.1999.0805

M3 - Article

C2 - 10865991

AN - SCOPUS:0033836933

SN - 0014-4835

VL - 70

SP - 429

EP - 439

JO - Experimental Eye Research

JF - Experimental Eye Research

IS - 4

ER -

Pharmacodynamics of beta-blocker modulation of aqueous humor production

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this