University of SaskatchewanHARVEST
  • Login
  • Submit Your Research
  • About
    • About HARVEST
    • Guidelines
    • Browse
      • All of HARVEST
      • Communities & Collections
      • By Issue Date
      • Authors
      • Titles
      • Subjects
      • This Collection
      • By Issue Date
      • Authors
      • Titles
      • Subjects
    • My Account
      • Login
      JavaScript is disabled for your browser. Some features of this site may not work without it.
      View Item 
      • HARVEST
      • Electronic Theses and Dissertations
      • Graduate Theses and Dissertations
      • View Item
      • HARVEST
      • Electronic Theses and Dissertations
      • Graduate Theses and Dissertations
      • View Item

      Role of methylglyoxal in the pathogenesis of hypertension

      Thumbnail
      View/Open
      wang_x.pdf (1.875Mb)
      Date
      2007
      Author
      Wang, Xiaoxia
      Type
      Thesis
      Degree Level
      Doctoral
      Metadata
      Show full item record
      Abstract
      Methylglyoxal (MG), a metabolite of glucose, causes non-enzymatic glycation of proteins to form irreversible advanced glycation end products (AGEs). Increased MG production, which in turn gives rise to AGEs, has been linked to the development of complications in diabetes. However, the role of MG and AGEs in hypertension has not been investigated widely. The previous study from our laboratory showed that the cellular levels of MG and MG-induced AGE formation are significantly higher in cultured aortic smooth muscle cells from spontaneously hypertensive rats (SHR) than those from normotensive Wistar-Kyoto rats (WKY). Using immunofluorescence staining with specific monoclonal antibodies against MG-induced AGEs, the present studies show a strong association of MG and its AGE products (Nå-carboxyethyl-lysine and Nå-carboxymethyl-lysine) with hypertension in SHR. The blood pressure of SHR was not different from that of WKY rats at 5 wks of age. From 8 wks onwards, blood pressure was significantly elevated compared to age-matched WKY rats. Importantly, this increase in blood pressure coincided with an elevated MG level in plasma and aorta of SHR in an age-dependent fashion compared to age-matched WKY rats, although no difference was observed in blood glucose levels between these two strains. Our data showed an increased MG level in plasma and aorta, but not in kidney or heart, in SHR at an early age of 8 wks, suggesting, in addition to diabetes/hyperglycemic or hyperlipidemic conditions, the accumulation of MG in blood vessel walls plays an important role in the development of hypertension or its complications even in the absence of diabetes. Moreover, we observed increased blood pressure and vascular remodeling in Sprague Dawley rats which had been treated to increase endogenous MG and related AGEs. After inhibiting MG and MG-induced AGE generation in SHR, hypertension development in this genetic hypertension model was delayed and vascular remodeling was reversed. Our data indicate that increased MG and AGE formation may play an important role in the development of hypertension.
      Degree
      Doctor of Philosophy (Ph.D.)
      Department
      Pharmacology
      Program
      Pharmacology
      Supervisor
      Wu, Lily
      Committee
      Tuchek, John M.; Hiebert, Linda M.; Hickie, Robert A.; Desai, Kaushik; deBlois, Denis; Yu, Peter H.
      Copyright Date
      2007
      URI
      http://hdl.handle.net/10388/etd-12132007-230430
      Subject
      rats
      Methylglyoxal
      hypertension
      Advanced glycation endproducts
      Collections
      • Graduate Theses and Dissertations
      University of Saskatchewan

      University Library

      © University of Saskatchewan
      Contact Us | Disclaimer | Privacy