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
      • College of Graduate and Postdoctoral Studies
      • Electronic Theses and Dissertations
      • View Item
      • HARVEST
      • College of Graduate and Postdoctoral Studies
      • Electronic Theses and Dissertations
      • View Item

      Effects of heme-l-arginate on L-NAME-induced hypertension

      Thumbnail
      View/Open
      L-THESIS.pdf (736.0Kb)
      Date
      2012-10-22
      Author
      L, Nina
      Type
      Thesis
      Degree Level
      Masters
      Metadata
      Show full item record
      Abstract
      N-ω-nitro-L-arginine methyl ester (L-NAME) has been used to induce experimental essential hypertension characterized by stimulation of the renin-angiotensin system (RAS) and oxidative system. Although the heme oxygenase (HO) system is known to suppress hypertension and the RAS, its effects on L-NAME-induced hypertension are poorly understood. Therefore, this study investigates the effects of heme-L-arginate (HA), a HO inducer, on L-NAME induced hypertension. HA (15mg/kg/day) was administered for 4 weeks either during the development or after the establishment (4 weeks) of L-NAME-induced (60mg/kg/day) hypertension in Sprague-Dawley (SD) rats. Vehicle control groups were used. Co-treatment with HA prevented the development of L-NAME induced hypertension, (124 mmHg, n=13 vs 168; n=10, 11 weeks; p<0.05). After L-NAME-induced hypertension was established for 4 weeks, HA therapy reduced blood pressure to normotensive at 15 weeks (123 mmHg, n=8 vs. 190 mmHg, n=7; (p<0.01). The prevention of hypertension was associated with increased HO-1 expression at 11 weeks (92.2±9.8 vs 15.9±9.9 HO-1/GAPDH %, n=4; p<0.01), reduction of heart Ang-II at 11 and 15 weeks (2.13±0.4 pg/mg, n=6 vs 4.06±0.4 pg/mg, n= 8; p<0.05 and 3.45±0.2 pg/mg, n=7 vs 4.23±0.2, n=7; p<0.05), respectively. HA co-treatment increased total antioxidant capacity (TAC) in heart tissue, the mesenteric artery and kidney. We conclude that up-regulating the HO system with HA normalizes blood pressure and prevents the development of L-NAME induced hypertension by suppressing Ang-II and abating oxidative stress. HA may be explored in the prevention and management of other forms hypertension characterized by elevated Ang-II and excessive oxidative stress.
      Degree
      Master of Science (M.Sc.)
      Department
      Physiology
      Program
      Physiology
      Supervisor
      Ndisang, Joseph F.
      Committee
      Desautels, Michel; West, Nigel; Alcorn, Jane
      Copyright Date
      August 2012
      URI
      http://hdl.handle.net/10388/ETD-2012-08-667
      Subject
      heme-l-arginate heme-oxygenase
      N-ω-nitro-L-arginine methyl ester
      Collections
      • Electronic Theses and Dissertations
      University of Saskatchewan

      University Library

      © University of Saskatchewan
      Contact Us | Disclaimer | Privacy