49. Mechanisms of vasoconstriction and vasodilatation

Last updated on October 6, 2020 at 12:46

We’ve talked a lot about vasoconstriction and vasodilation, but we haven’t yet discussed how these processes occur.

Vessels have varying amount of smooth muscle in their walls, especially the arteries and arterioles. Vasoconstriction occurs when this smooth muscle contracts, and vasodilation occurs when this smooth muscle relaxes. I won’t describe the exact mechanism of smooth muscle contraction, but I will describe how different vasodilators and vasoconstrictors cause their effects.

Some compounds, most notably epinephrine, can be both a vasodilator and a vasoconstrictor, depending on the tissue. In the skin and splanchnic circulation epinephrine binds to alpha-1 receptors, which causes vasoconstriction. In the skeletal muscle epinephrine binds to beta-2 receptors, causing vasodilation.

Smooth muscle contraction

For smooth muscle to contract the intracellular level of Ca2+ must increase. This is can be achieved by two ways:

  • By opening calcium channels on the surface of the cell, which allows extracellular Ca2+ to enter the cytoplasm
  • By opening calcium channels on the sarcoplasmic reticulum, which allows Ca2+ inside the reticulum to enter the cytoplasm

The increased Ca2+ level will activate a protein called calmodulin. Activated calmodulin will activate another protein called myosin light chain kinase (MLCK). MLCK will then phosphorylate the myosin head which causes the contraction.

Different vasoconstrictors and vasodilators act on smooth muscle cells in different ways to either increase or decrease the intracellular level of Ca2+, respectively.

Catecholamines, thromboxane, endothelin, angiotensin II, vasopressin

These vasoconstrictors all act by the same mechanism. They all bind to so-called Gq-coupled receptors on the cell surface. Their binding to the receptor initiates a cascade of processes inside the cell:

  1. The vasoconstrictor binds to its cell surface receptor
  2. The Gq protein inside the cell is activated
  3. The enzyme phospholipase C is activated
  4. Phospholipase C cleave phospholipids into two molecules, DAG and IP3
  5. DAG and IP3 open calcium channels on the sarcoplasmic reticulum
  6. The cytoplasmic Ca2+ level increases
  7. Contraction
Stretch

As explained earlier, the Bayliss effect causes vessels to vasoconstrict when stretched. This effect is achieved like this:

  1. The stretching of the smooth muscle cell causes special stretch-activated ion channels to open
  2. The smooth muscle cell is depolarized
  3. Voltage-gated calcium channels open, causing extracellular Ca2+ to enter the cell
  4. The cytoplasmic Ca2+ level increases
  5. Contraction
Nitric oxide

Nitric oxide (NO) is a powerful vasodilator. It is synthesized by endothelium. Because NO is a gas it doesn’t need to bind to a receptor on the surface of the smooth muscle cell as it can simply diffuse into the cell.

  1. NO diffuses into the smooth muscle cell
  2. NO activates an enzyme called guanylate cyclase inside the cell
  3. Guanylate cyclase converts GTP to cGMP
  4. cGMP activates an enzyme called protein kinase G
  5. Protein kinase G closes calcium channels, preventing calcium from entering the cell
  6. Protein kinase G also phosphorylates myosin light chain kinase, inhibiting it
  7. Relaxation
Epinephrine, histamine, prostacyclin

These vasodilators act by a different pathway than NO. They all bind to so-called Gs-coupled receptors on the cell surface.

  1. The vasodilator binds to its cell surface receptor
  2. The Gs receptor inside the cell is activated
  3. The enzyme adenylate cyclase is activated
  4. Adenylate cyclase converts ATP to cAMP
  5. cAMP activates a protein called protein kinase A
  6. Protein kinase A closes calcium channels, preventing calcium from entering the cell
  7. Protein kinase A also phosphorylates myosin light chain kinase, inhibiting it
  8. Relaxation

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48. Reflex control mechanisms of circulation

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50. Mechanics of respiration (functions of respiratory muscles, compliance, intrathoracic pressures, respiratory volumes)

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