Endothelial Cells Can Release Chemicals That Cause Relaxation or Constriction of Arterioles

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An important contributor to local vascular regulation is released by endothelial cells. This substance, endothelium-derived relaxing factor (EDRF), is released from all arteries, microvessels, veins, and lymphatic endothelial cells. EDRF is nitric oxide (NO), which is formed by the action of nitric oxide synthase on the amino acid arginine. NO causes the relaxation of vascular smooth muscle by inducing an increase in cyclic guanosine monophosphate (cGMP). When cGMP is increased, the smooth muscle cell extrudes calcium ions and decreases calcium entry into the cell, inhibiting contraction and enzymatic processes that depend on calcium ions. Compounds such as acetylcholine, histamine, and adenine nucleotides (ATP, ADP) released into the interstitial space, as well as hypertonic conditions and hypoxia cause the release of NO. Adenosine causes NO release from endothelial cells and directly relaxes vascular smooth muscle cells through adenosine receptors.

Another important mechanism to release NO is the shear stress generated by blood moving past the endothe-lial cells. Frictional forces between moving blood and the stationary endothelial cells distort the endothelial cells, opening special potassium channels and causing endothe-lial cell hyperpolarization. This increases calcium ion entry into the cell down the increased electrical gradient. The elevated cytosolic calcium ion concentration activates en-dothelial nitric oxide synthase to form more NO, and the blood vessels dilate.

This mechanism is used to coordinate various sized arte-rioles and small arteries. As small arterioles dilate in response to some signal from the tissue, the increased blood flow increases the shear stress in larger arterioles and small arteries, which prompts their endothelial cells to release NO and relax the smooth muscle. As larger arterioles and small arteries control much more of the total vascular resistance than do small arterioles, the cooperation of the larger resistance vessels is vital to adjusting blood flow to the needs of the tissue. Examples of this process, called flow-mediated vasodilation, have been observed in cerebral, skeletal muscle, and small intestinal vasculatures. Endothelial cells of arterioles also release vasodilatory prostaglandins when blood flow and shear stress are increased. However, NO appears to be the dominant vasodilator molecule for flow-dependent regulation. Clinical Focus Box 16.1 describes the defects in endothelial cell function and NO production that are a major contribution to the pathophysiology of diabetes mellitus.

Endothelial cells also release one of the most potent vasoconstrictor agents, the 21 amino acid peptide endothelin. Extremely small amounts are released under natural conditions. Endothelin is the most potent biological constrictor of blood vessels yet to be found. The vasoconstriction occurs because of a cascade of events beginning with phospholipase C activation and leading to activation of protein kinase C (see Chapter 1). Two major types of endothelin receptors have been identified and others may exist. The constrictor function of endothelin is mediated by type B endothelin receptors. Type A endothelin receptors cause hyperplasia and hypertrophy of vascular muscle cells and the release of NO from endothelial cells. The precise function of endothelin in the normal vasculature is not clear,- however, it is active during embryological development. In knockout mice, the absence of the endothelin A receptor results in serious cardiac defects so newborns are not viable. An absence of the type B receptor is associated with an enlarged colon, eventually leading to death. Endothelin clearly has functions other than vascular regulation.

In damaged heart tissue, such as after poor blood flow resulting in an infarct, cardiac endothelial cells increase endothelin production. The endothelin stimulates both vascular smooth muscle and cardiac muscle to contract more vigorously and induces the growth of surviving cardiac cells. However, excessive stimulation and hypertrophy of cells appears to contribute to heart failure, failure of contractility, and excessive enlargement of the heart. Part of the stimulation of endothelin production in the injured heart may be the damage per se. Also, increased formation of angiotensin II and norepinephrine during chronic heart disease stimulates endothelin production, probably at the gene expression level. Activation of protein kinase C (PKC) increases the expression of the c-jun proto-onco-gene, which, in turn, activates the preproendothelin-1 gene. Endothelin has also been implicated as a contributor to renal vascular failure, both pulmonary hypertension and the systemic hypertension associated with insulin resistance, and the spasmodic contraction of cerebral blood vessels exposed to blood after a brain injury or stroke associated with blood loss to brain tissue.

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  • barbara
    What is vasoconstrictor chemical released by endothelial cells?
    8 years ago
  • Alem
    Is adenosine the vasodilator substance released by cardiac cells?
    7 years ago
  • michal
    What does endothelial cells release?
    6 years ago
  • mari
    What is released from endothelial to cause arteries to relax upstream of endothelial?
    5 years ago
  • Walter
    What are the chemicals released by endothelial cells to cause vasoconstriction?
    2 years ago
  • derek
    What substance is secreted by endothelial cells?
    2 years ago
  • Bonnie
    What chemical in the muscles cause them to relax?
    2 years ago
  • Layton
    What substance is released from the endothelia to cause vessel smooth muscle relaxation?
    1 year ago
  • amalia
    What do hotels do to cause relaxation?
    12 months ago
    What substance released from damaged endothelium triggers?
    9 months ago
    What chemicals do healthy endothelial cells release and what is their function?
    9 months ago
  • Matthias
    What chemicals released by skeletal muscle in heart failure?
    6 months ago
  • stanislao
    How does histamine release calcium into muscle cells?
    4 months ago
  • topi
    How do endothelial cells cause smooth muscle relxation?
    12 days ago

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