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L. Wagenfeld, B. Becker, P. Galambos, E.T. Matthiessen, G. Richard, M. Klemm, O. Zeitz; The Influence of Carbonic Anhydrase Inhibitors on the Tone of the Posterior Ciliary Arteries in Porcine Eyes . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4719.
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Purpose: Inhibitors of the carbonic anhydrase are important drugs for glaucoma treatment. Vaso–relaxing properties and subsequently beneficial effects on ocular perfusion have been proposed for some compounds of this group. This effect could not be attributed to pH changes caused by the inhibition of the carbonic anhydrase, because some compounds like dorzolamide show these effects while others do not or at least do not that pronounced. Thus the aim of the current study is to examine direct effects of different carbonic anhydrase inhibitors on muscle fibres of the posterior ciliary arteries. Methods: Rings of the posterior ciliary arteries were dissected from porcine eyes, which were obtained from a slaughterhouse. In a setup for measurement of muscle force the basal tone of the vessels and the maximum force after potassium–depolarisation where measured in a physiological environment (pH 7.4, 37°C, Krebs–Henseleit–Buffer) without and with acetazolamide (Sigma Chemicals) or dorzolamide (received as a gift from MSD Sharp&Dohme, Munich, Germany). After Bonferoni adjustment p–values < 0,0083 (t–test; double–sided) were considered to be significant. Results: Force provoked by K+–depolarisation did not change in presence of 10–6 and 10–5 M Dorzolamide (D.) (4,0 ± 0,7 mN without D. vs. 4,1 ± 0,8 mN with 10–6 M D. [n=9, p=0,49]; 3,9 ± 1,3 mN without D. vs. 4,5 ± 1,6 mN with 10–5 M D. [n=9, p=0,19]). 10–6 and 10–5 M Acetazolamide (A.) also did not influence maximal force development significantly (3,8 ± 0,8 mN without A. vs. 4,1 ± 0,8 mN with 10–6 M A. [n=17, p=0,01]; 4,3 ± 0,7 mN without A. vs. 4,3 ± 0,7 mN with 10–5 M A. [n=15, p=0,73]). Similar to developed force in depolarized preparations, basal tone was not influenced, neither by dorzolamide nor by acetazolamide (–0,2 ± 0,04 mN in control group vs. –0,2 ± 0,05 mN under 10–5 M A. [n=14, p=0,08]; –0,2 ± 0,04 mN in control group vs. –0,3 + 0,08 mN under 10–5 M D. [n=9, p=0,07]). In the control group force was also stable in two subsequent depolarisations (n=11, p=0,22). Conclusions: In the present setting no functional effect on vascular muscle preparations could be found. This makes a direct interaction between the compounds and the myofilaments unlikely. Thus further investigations will be necessary to explain different clinical results for different inhibitors of the carbonic anhydrase concerning their effect on ocular perfusion. Potentially these compounds interact with endothelium or adrenergic signalling pathways.
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