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Dorzolamide-induced relaxation of isolated rabbit ciliary arteries mediated by inhibition of extracellular calcium influx

  • Laboratory Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

The carbonic anhydrase inhibitor dorzolamide can increase optic nerve blood flow. The aim of the study reported here was to investigate the effect of dorzolamide on isolated rabbit ciliary arteries that supply the optic nerve.

Methods

Changes in ciliary artery isometric tension and intracellular Ca2+ concentration ([Ca2+]i) were recorded to elucidate the underlying pharmacologic mechanisms by which dorzolamide regulates blood flow to the optic nerve.

Results

Dorzolamide induced concentration-dependent relaxation of rabbit ciliary arteries that had been precontracted by exposure to a high potassium (high-K) solution. Neither pretreatment with 10 µM KB-R 7943, an Na+/Ca2+ exchanger inhibitor, nor alkalinization of the high-K solution had an effect on the dorzolamide-induced relaxation. Pretreatment with 100 µM NG-nitro-l-arginine methylester, a nitric oxide synthase inhibitor (n = 10), 10 µM indomethacin, a prostacyclin inhibitor (n = 9), or 0.1 µM iberiotoxin, an inhibitor of endothelium-derived hyperpolarizing factor (n = 7), did not change the concentration-dependent relaxation induced by dorzolamide. Incubation with 3 mM dorzolamide in a Ca2+-free solution did not change the transient contractions of the rabbit ciliary arteries induced by 1 µM histamine (n = 9). However, 3 mM dorzolamide significantly suppressed the increase in [Ca2+]i induced by the reintroduction of Ca2+ to a calcium-free extracellular medium (P < 0.05). Furthermore, 3 mM dorzolamide significantly suppressed the [Ca2+]i increase induced by the high-K solution (P < 0.05).

Conclusions

Taken together, our results reveal a novel role for dorzolamide in relaxing the ciliary arteries. Our data support the hypothesis that the vasodilatory action of dorzolamide is mediated by inhibition of Ca2+ entry through voltage-dependent Ca2+ channels.

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Acknowledgments

The authors thank Ms. Sanae Takaseki for her excellent technical assistance. This study was supported by a Japan Society for the Promotion of Science (JSPS) grant-in-aid for scientific research ([C] 25462750).

Conflicts of interest

Y. Dong, None; Y. Sawada, None; J. Cui, None; M. Hayakawa, None; D. Ogino, None; M. Ishikawa, None; T. Yoshitomi, None.

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Authors and Affiliations

  1. Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan

    Yaru Dong, Yu Sawada, Masahiro Hayakawa, Dai Ogino, Makoto Ishikawa & Takeshi Yoshitomi

  2. Department of Ophthalmology, The Second Hospital of Jilin University, Jilin, China

    Yaru Dong & Jizhe Cui

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  1. Yaru Dong
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  2. Yu Sawada
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Correspondence to Takeshi Yoshitomi.

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Dong, Y., Sawada, Y., Cui, J. et al. Dorzolamide-induced relaxation of isolated rabbit ciliary arteries mediated by inhibition of extracellular calcium influx. Jpn J Ophthalmol 60, 103–110 (2016). https://doi.org/10.1007/s10384-015-0423-z

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  • DOI: https://doi.org/10.1007/s10384-015-0423-z

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