title: Tunicamycin-Induced Alterations in the Vasorelaxant Response in Organ-Cultured Superior Mesenteric Arteries of Rats.
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.
authors: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University.
authors: Takayuki
authors: T
authors: Matsumoto
authors: Makoto
authors: M
authors: Ando
authors: Shun
authors: S
authors: Watanabe
authors: Maika
authors: M
authors: Iguchi
authors: Mako
authors: M
authors: Nagata
authors: Shota
authors: S
authors: Kobayashi
authors: Kumiko
authors: K
authors: Taguchi
authors: Tsuneo
authors: T
authors: Kobayashi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress; D004730:Endothelium, Vascular / Q000502:physiology; D006360:Heat-Shock Proteins / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009924:Organ Culture Techniques; D017208:Rats, Wistar; D014415:Tunicamycin / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000109:Acetylcholine; D000900:Anti-Bacterial Agents; D005576:Colforsin; D019806:Cromakalim; D006360:Heat-Shock Proteins; D007545:Isoproterenol; D009569:Nitric Oxide; D009599:Nitroprusside; D014415:Tunicamycin; D014665:Vasodilator Agents; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP