University of SaskatchewanHARVEST
  • Login
  • Submit Your Work
  • 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

      Vasodilator and antihypertensive effects of l-serine

      Thumbnail
      View/Open
      MishraRC-Thesis.pdf (2.791Mb)
      Date
      2009
      Author
      Mishra, Ramesh Chandra
      Type
      Thesis
      Degree Level
      Doctoral
      Metadata
      Show full item record
      Abstract
      L-serine, a non-essential amino acid, plays a role in the biosynthesis of the amino acids, proteins, purine and pyrimidine nucleotides. It is important for the proper functioning of the nervous system. It has been considered in the treatment of patients with schizophrenia, depression, chronic fatigue syndrome and psychomotor retardation, and of the seizures encountered in patients with rare inborn errors of L-serine biosynthesis. However, there are no reports in the literature of the direct cardiovascular effects of L-serine. Using normotensive Sprague-Dawley rats, Sprague-Dawley rats rendered hypertensive by chronic treatment with the nitric oxide (NO) synthase inhibitior NG nitro L-arginine methyl ester (L-NAME) and spontaneously hypertensive rats (SHR), the present study examined the in vitro and in vivo effects of L-serine. In vitro studies focused on L-serine induced changes in phenylephrine constricted third order branches of rat mesenteric arterioles while the in vivo studies examined the effects of intravenous infusion of L-serine on mean arterial pressure (MAP) and heart rate (HR) in intact anaesthetized rats. L-serine (10 to 200 µmol/L) evoked concentration-dependent vasodilatation in phenylephrine constricted endothelium-intact, but not in endothelium-denuded, rat mesenteric arterioles. The vasodilator responses to L-serine were absent in the combined presence of apamin, a calcium activated small conductance potassium (SKCa) channel inhibitor, and TRAM-34, a calcium activated intermediate conductance potassium (IKCa) channel inhibitor, or ouabain, a sodium pump inhibitor and barium (Ba2+), an inward rectifying potassium (Kir) channel inhibitor, or when the vessels were depolarized by potassium chloride. The maximal vasodilatation response (Emax) to L-serine was higher in vessels from L-NAME treated rats (40%) than from control rats (20%). In anesthetized rats, L-serine evoked a rapid, reversible, dose-dependent fall in MAP (without a significant change in HR), which was more pronounced in L-NAME treated rats (> 60 mmHg) than in normotensive control rats (25 mmHg). The fall in MAP was inhibited (p
      Degree
      Doctor of Philosophy (Ph.D.)
      Department
      Pharmacology
      Program
      Pharmacology
      Supervisor
      Gopalakrishnan, Venkat
      Copyright Date
      2009
      URI
      http://hdl.handle.net/10388/etd-07152009-104447
      Subject
      Amino acids
      Blood pressure
      L-serine
      Glycine
      Vasodilation
      Hypertension
      Mean arterial pressure
      Collections
      • Graduate Theses and Dissertations
      University of Saskatchewan

      University Library

      © University of Saskatchewan
      Contact Us | Disclaimer | Privacy