Involvement of Gap Junctions in Acetylcholine-Induced Endothelium-Derived Hyperpolarization-Type Dilation of Retinal Arterioles in Rats

• Mori Asami

  Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences

• Namekawa Ryo

  Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences

• Sakamoto Kenji

  Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences

• Ishii Kunio

  Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences

• Nakahara Tsutomu

  Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences

Abstract

An electrical communication between the endothelial and smooth muscle cells via gap junctions, which provides the signaling pathway known as endothelium-dependent hyperpolarization (EDH), plays a crucial role in controlling the vascular tone. In this study, we investigated the role of gap junctions in the acetylcholine (ACh)-induced EDH-type dilation of rat retinal arterioles in vivo. The dilator response was evaluated by measuring the diameter of retinal arterioles. Intravitreal injection of gap junction blockers (18β-glycyrrhetinic acid and carbenoxolone) reduced the ACh-induced dilation of retinal arterioles. Moreover, the retinal arteriolar response to ACh was attenuated by 18β-glycyrrhetinic acid under treatment with a combination of N^G-nitro-L-arginine methyl ester (a nitric oxide (NO) synthase inhibitor; 30 mg/kg) and indomethacin (a cyclooxygenase inhibitor; 5 mg/kg). The NO- and prostaglandin-independent, EDH-related component of ACh-induced dilation of retinal arterioles was prevented by intravitreal injection of iberiotoxin, which inhibits large-conductance Ca²⁺-activated K⁺ channels. Furthermore, the combination of 18β-glycyrrhetinic acid and iberiotoxin produced greater attenuation in the EDH-related response than that by the individual agent. Treatment with 18β-glycyrrhetinic acid revealed no significant effect on NOR3 (an NO donor)-induced retinal vasodilator response. These results suggest that gap junctions contribute to the ACh-induced, EDH-type dilation of rat retinal arterioles in vivo.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 44 (12), 1860-1865, 2021-12-01

  The Pharmaceutical Society of Japan

Keywords

• endothelium-dependent hyperpolarization
• gap junction
• nitric oxide
• prostaglandin
• retina
• vasodilation

Details

• CRID: 1390571713984078080
• NII Article ID: 130008123493
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.b21-00547
• ISSN: 13475215
• ISSN: 09186158
• NDL BIB ID: 031837958
• Web Site: http://id.ndl.go.jp/bib/031837958
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I031837958
• Web Site: https://www.jstage.jst.go.jp/article/bpb/44/12/44_b21-00547/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2023019134
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed