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Research ArticleArticle

Timolol Effects on Aqueous Humor Dynamics in Eyes of Anesthetized Rats

Robin V. Searles, Vladimir Shikher, Carey D. Balaban and Walter B. Severs
Journal of Pharmacology and Experimental Therapeutics February 1999, 288 (2) 838-842;
Robin V. Searles
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Vladimir Shikher
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Carey D. Balaban
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Walter B. Severs
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Abstract

Anterior chambers of the eyes of male rats were cannulated under pentobarbital anesthesia for intracameral infusions of balanced salt solution (BSS) and intraocular pressure (IOP) recording. Blood pressure was recorded from a femoral artery. IOP was recorded during a 2-h intracameral infusion composed of a constant component (0.05 μl/min) and a periodic component (0.25 μl/min), cycling at 4 min on and then 4 min off. After a 20-min baseline period, 1 drop of timolol (0.5%) or BSS was applied to the cornea and repeated 1 h later. Intracameral infusions of BSS and 0.05% timolol were also compared. Topical timolol slightly delayed the BSS-induced IOP rise (p < .05). Complex demodulation and the estimated gain parameter of a second-order transfer function fit to the periodic responses revealed that topical timolol also reduced (p < .05) passive outflow resistance. Intracameral timolol markedly delayed the BSS-induced rise in IOP. Initially, timolol decreased both outflow impedance and nonresistive components (p < .05) of IOP, but these effects dissipated by 2 h when IOPs were similar. In all experiments, within-group blood pressure was unchanged. Topical and intracameral timolol have different effects on IOP. The data support the opinion that, in vivo, timolol acts at β-receptors that control both outflow impedance and nonresistive mechanisms, probably vascular, to lower IOP.

Footnotes

  • Send reprint requests to: Walter B. Severs, Department of Pharmacology, H078, Hershey Medical Center, Hershey, PA 17033. E-mail:wbs2{at}psu.edu

  • ↵1 Supported in part by National Aeronautics and Space Administration Award NSG-UMF-93018. Preliminary abstracts appeared in FASEB J 11:A202 (1997) and J Clin Pharmacol 36:861 (1996).

  • Abbreviations:
    BSS
    balanced salt solution
    IOP
    intraocular pressure
    BP
    mean arterial blood pressure
    Ao
    passive resistance to aqueous humor drainage along the trabecular and uveoscleral outflow pathways
    RP
    residual pressure, unexplained by analysis, that encompasses aqueous humor synthesis rate and episcleral venous pressure
    • Received May 22, 1998.
    • Accepted September 16, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 2
1 Feb 1999
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Research ArticleArticle

Timolol Effects on Aqueous Humor Dynamics in Eyes of Anesthetized Rats

Robin V. Searles, Vladimir Shikher, Carey D. Balaban and Walter B. Severs
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 838-842;

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Research ArticleArticle

Timolol Effects on Aqueous Humor Dynamics in Eyes of Anesthetized Rats

Robin V. Searles, Vladimir Shikher, Carey D. Balaban and Walter B. Severs
Journal of Pharmacology and Experimental Therapeutics February 1, 1999, 288 (2) 838-842;
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