Importance of endothelial function

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  • Importance of endothelial function
    • Arteries: conduit (elastic), muscular (distributing)
    • ACh: vasorelaxant
    • EDRF: endothelium derived relaxant factor
      • Stimlulus for basal release is flow. Cell surface senses shear stress > intracellular signalling events > release
      • Shown to be NO
        • NO production: agonist stimulated
        • Secreted by endothelium
        • Enzyme: eNOS, Precursor: L-arginine, Co-factor: BH4
          • Activation of eNOS follows a rise in intracellular calcium
        • NO increases production of cGMP, which reverses vasoconstriction
        • NO decreases: SM contraction, platelet aggrevation, LDL oxidation, expression of adhesion molecules, platelet adhesion
      • Gap junction dependent
    • Function of endothelium: Regulation of: haemostasis, angiogenesis, permeability, inflammation, vascular tone, synthesis and release of factors
    • LDL undergoes oxidative modification with intima and becomes ox LDL
      • Develops at arterial branches and sites of curvature / bifurcation: regions of low and disturbed wall shear stress
        • Disturbed flow leads to decrease in: eNOS production, vasodilation, endothelial cell repair
    • Endothelium: monolayer forming lumen of all blood vessels
      • Releases vasoactive agents that control functions e.g tone and haemostasis
      • Dysfunction: looses tightly regulated balance > vasospasm and atherosclerosis > CHD, hypertension, stroke
  • Oxidative stress reduces effects / bioavailability of NO.. May produce superoxide O2-, producing peroxynitrate ONOO-
    • Peroxynitrate interacts with lipids, DNA and proteins

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