title: Diabetes and Age-Related Differences in Vascular Function of Renal Artery: Possible Involvement of Endoplasmic Reticulum Stress.
abstract: To study the time-course relationship between vascular functions and endoplasmic reticulum (ER) stress in type 2 diabetes, we investigated vascular function and associated protein expression, including cyclo-oxygenase (COX), ER stress, and apoptotic markers, in renal arteries (RA) from type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats at the young adult (4 months old) and aged (18 months old) stages. In the RA of aged OLETF (vs. young OLETF), we found: (1) Increased contractions induced by uridine adenosine tetraphosphate (Up4A) and phenylephrine, (2) decreased relaxation and increased contraction induced by acetylcholine (ACh) at lower and higher concentrations, respectively, and (3) increased expression of COX-1 and C/EBP-homologous protein (CHOP, a pro-apoptotic protein). In aged rats, the expression of COX-1, COX-2, PDI (an ER protein disulfide isomerase), Bax (a proapoptotic marker), and CHOP were increased in RA from OLETF rats (vs. age-matched control Long-Evans Tokushima Otsuka [LETO] rats). Up-regulation of PDI and Bax were seen in the RA from young OLETF (vs. young LETO) rats. No age-related alterations were apparent in the above changes in RA from LETO rats, excluding ACh-induced contraction. Short-term treatment with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 100 mg/kg per day, intraperitoneally for 1 week) to OLETF rats at the chronic stage of the disease (12 months old) could suppress renal arterial contractions induced by Up4A and ACh. These results suggest that a long-term duration of disease may be important for the development of vascular dysfunction rather than aging per se. The early regulation of ER stress may be important against the development of diabetes-associated vascular dysfunction.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku, Tokyo, Japan .
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku, Tokyo, Japan .
authors.forename: Shun
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku, Tokyo, Japan .
authors.forename: Makoto
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku, Tokyo, Japan .
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku, Tokyo, Japan .
authors.forename: Maika
authors.initials: M
authors.lastname: Iguchi
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku, Tokyo, Japan .
authors.forename: Kumiko
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku, Tokyo, Japan .
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology*; D015226:Dinucleoside Phosphates / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D012077:Renal Artery / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D056564:Sirtuin 1 / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015226:Dinucleoside Phosphates; D051028:bcl-2-Associated X Protein; C529314:uridine adenosine tetraphosphate; D009599:Nitroprusside; D010656:Phenylephrine; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D011451:Prostaglandin-Endoperoxide Synthases; D054513:Group IV Phospholipases A2; D056564:Sirtuin 1; D000109:Acetylcholine