Tunicamycin-induced alterations in the vasorelaxant response in organ-cultured superior mesenteric arteries of rats

Takayuki Matsumoto, Makoto Ando, Shun Watanabe, Maika Iguchi, Mako Nagata, Shota Kobayashi, Kumiko Taguchi, Tsuneo Kobayashi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

In cellular events, endoplasmic reticulum (ER) stress has an important role in the development of various diseases including cardiovascular diseases. Tunicamycin, an inhibitor of N-linked glycosylation, is known to be an inducer of ER stress. However, the extent to which tunicamycin affects the vasorelaxant function is not completely understood. Thus, we investigated the effect of tunicamycin on relaxations induced by various vasorelaxant agents, including acetylcholine (ACh; endothelium-dependent vasodilator), sodium nitroprusside (SNP; endothelium-independent vasodilator), isoprenaline (ISO; beta- Adrenoceptor agonist), forskolin (FSK; adenylyl cyclase activator), and cromakalim [ATP-sensitive K+ (KATP) channel activator] in organ-cultured superior mesenteric arteries of rats, which are treated with either a vehicle [dimethyl sulfoxide (DMSO)] or tunicamycin (20 μg/mL for 22-24 h). Protein levels of the ER stress marker binding immunoglobulin protein (BiP) were determined by Western blotting. Tunicamycin increased the expression of BiP in organ-cultured arteries. Tunicamycin impaired ACh-induced relaxation, but did not alter SNP-induced relaxation. Tunicamycin also impaired vasorelaxation induced by ISO, FSK, and cromakalim; moreover, it reduced basal nitric oxide (NO) formation. In conclusion, short- Term treatment with tunicamycin not only caused endothelial dysfunction but also impaired cAMP- And KATP-mediated responses in the superior mesenteric arteries of rats. These alterations in tunicamycin- Treated arteries may be due to reduced basal NO formation. This work provides new insight into ER stress in vascular dysfunction.

Original languageEnglish
Pages (from-to)1475-1481
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume39
Issue number9
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • Endoplasmic reticulum stress
  • Mesenteric artery
  • Relaxation
  • Tunicamycin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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