title: Age-Related Reduction of Contractile Responses to Urotensin II Is Seen in Aortas from Wistar Rats but Not from Type 2 Diabetic Goto-Kakizaki Rats.
abstract: Vascular dysfunction is a common finding in type 2 diabetes, although the response to urotensin II (UII), a potent vasoconstrictor peptide, remains unclear. We investigated whether a UII-induced contraction was increased in the aortas from type 2 diabetic Goto-Kakizaki (GK) rats at the chronic stage. At 36 or 37 weeks of age (older group), a UII-induced contraction was seen in GK rats and was reduced by a Rho kinase inhibitor or urotensin receptor (UT) antagonist, whereas UII failed to induce a contraction in aortas from age-matched Wistar rats. In UII-stimulated aortas, the expression of Rho kinases, Rho A, and phosphorylated myosin phosphatase target subunit 1 did not change between the two groups; however, phosphorylation of extracellular-regulated kinase 1/2 and p38 mitogen-activated protein kinase (MAPK) was greater in GK than in Wistar rats. Compared to intact aortas, UII-induced contractions were slightly, but not significantly, increased by endothelial denudation of the aortas of Wistar rats at 24 weeks of age. At 6 weeks of age (young group), the UII-induced contractions were seen in GK and Wistar groups. The total expression and the membrane-to-cytosol ratio of the UT protein slightly decreased in Wistar aortas with aging but not in GK aortas. These results demonstrate that the UII-induced contraction gradually decreased with aging in Wistar rats and was preserved in type 2 diabetes. Although alterations of UII-induced contractions during aging and type 2 diabetes may be associated with kinase activities (MAPKs or Rho kinase) or receptor profiles, further investigations are necessary to clarify the mechanisms.
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: Shota
authors.initials: S
authors.lastname: Kobayashi
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: 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: D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015151:Immunoblotting; D009119:Muscle Contraction / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D014579:Urotensins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D047428:Protein Kinase Inhibitors; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C029677:urotensin II; D054460:rho-Associated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Rho kinase; UT receptor; contraction; type 2 diabetes; urotensin II