lecture 17



endothelial cells control vascular tone - smooth muscle contraction and relaxation


yellow structure - represent gap junctions

  • in many blood vessels there are numerous gap junctions between the endothelial cells and smooth muscle cells

  • not as many between endothelial and endothelial cells

  • smaller vessels tend to have more myoendothelial gap junctions


relaxation

  • nitric oxide an diffuse through cell membranes

  • PGI2 - exported from cell and acts on cell membrane receptor

  • EDHF - electrical communication by hyperpolarization


contraction

  • endothelin is a peptide

    • generated through transcription and translation, then exported from the cell and acts on a g coupled receptor




membrane potention is graded (-30 mV → -68 mV)

  • activated endothelial cells hyperpolarize


KIR - inward retifier potassium channel (keep MP negative)

  • open in negative membrane potentials





2 key events when EC are stimulated






  1. membrane potential (more negative) further away from equilibrium potential (124 mV? for calcium) - bigger driving force

  2. currents travel from EC → EC and also EC → SMC (many arteries and arterioles)



  1. nitric oxide synthase - enzyme that produces nitric oxide NO* (free radical)

    • nitric oxide diffuses to smooth muscle and causes vasodilation

  2. break adherens junctions and form gap to allow immune cells to come in






discovered first lol

PLA2 = phospholipase A2 (enzyme)

COX = cycloxygenase

  • category of drugs called cyclooxygenase inhibitors like aspirin






  1. puts the brakes on phenotypic changes that promote atherosclerosis

  2. ED recuit leokocytes (white blood cells) to repair damage, this can get out of control in atherosclerosis and cause an inflamed area of artery which promotes the atherosclerotic process

  3. during inflammation


anti-atherogenic - prevent atherosclerosis





Nitric Oxide Production is stimulated by Agonists or Shear Stress

eNOS is activated by

  1. increase in Ca2+ (Ca2+ - calmodulin binding)

  2. phosphorylation





EET will cause dilation/relaxation of smooth muscle



EDHF

increase in calcium → calcium acts on calcium activated potassiuum channels KCA

causes hyperpolarization → carried through to smooth muscle cells

hypoerpolarized SMC inhibits L-type calcium channels → Ca2+ levels in cell goes down → relaxation



large arteries dont have myoendothelial gap junctions → so no edhf







long lasting vasoconstrictor (2-3 hours)

particularly prominent in the lungs → pulmonary hypertension (dont need to know the others



ECE = endothelium converting enzyme

ET1 enters extracellular fluid, can then act on receptors (g coupled receptors 2 types)

both increase Ca++ in the cell → contraction


there are also endothelin receptors (ETB)on the membrane of EC

causes release of nitric oxide and prostacycline - blocks contraction

  • block ETB receptors → enhance contstriction by endothelin

  • block ETA receptors → reduce constriction by endothelin




*chronic shear stress

*LDL cholesterol

^ mostly vasoconstrictors that causes EC’s to produce more endophelin

  • almost like a positive feedback loop



*ANP = atrial natriuretic peptide





also involved in cardiac remodelng

increased in several pathologies