Cardiovascular physiology: Vasoconstriction & endothelial function
On this page
Most vasoconstrictors bind to G Protein, an important mediator in vasoconstriction, which triggers a rise in intracellular calcium ion (Ca 2+ ions) levels triggering vascular smooth muscle contraction.
The endothelium responds to a number of substances in the blood and changes in blood flow.
Important endothelium derived vasodilators and vasoconstrictors
Nitric oxide (NO) plays an important role in the continuous modulation of vascular tone. NO synthesis by the endothelium is stimulated by several mechanisms:
Endothelin-1 is an extremely potent vasoconstrictor and plays an important role in maintaining blood pressure. Its release by the endothelium is stimulated by the following (mainly other vasoconstrictors):
Prostacyclin and thromboxane A2 are eicosanoids (signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid).
Important vasoconstrictors:
- Endothelin 1
- Noradrenaline (norephinephrine)
- Angiotensin II
Clinical application
Calcium channel blockers decrease intracellular calcium levels resulting in vasodilatation - it is the rationale behind using them for people who have Raynauds.
Calcium channel blockers decrease intracellular calcium levels resulting in vasodilatation - it is the rationale behind using them for people who have Raynauds.
Endothelial function
Endothelium is very important in governing vascular tone synthesizing both vasoconstrictors and vasodilators.The endothelium responds to a number of substances in the blood and changes in blood flow.
Important endothelium derived vasodilators and vasoconstrictors
| Vasodilators | Vasoconstrictors |
|---|---|
| Nitric oxide (NO) Prostacyclin (PGI2) | Endothelin-1 Thromboxane A2 |
Nitric oxide (NO) plays an important role in the continuous modulation of vascular tone. NO synthesis by the endothelium is stimulated by several mechanisms:
- Factors that elevate intracellular calcium such as bradykinin, histamine and serotonin.
- Some neurotransmitters such as substance P
- Increased blood flow (increased shear stress)
Vasodilators
Vasodilators work by lowering the concentration of intracellular calcium.
Lowering intracellular calcium is typically achieved via:
Terminology
Mechanism
SERCA lowers intracellular calcium by sequestering calcium ions in the smooth ER whilst PMCA lowers calcium by pumping it out of the cell.
Vasodilators will stimulate SERCA and PMCA via secondary chemical messengers such as cGMP (e.g. nitrous oxide) and cAMP (e.g. prostacyclin) which in turn act by elevating protein kinase A and G (PKA and PKG).
Vasodilators work by lowering the concentration of intracellular calcium.
Lowering intracellular calcium is typically achieved via:
- Stimulation of SERCA and PMCA
- Hyperpolarizing cell membrane to inhibit L-type Ca2+ channels
Terminology
- SERCA: Smooth Endoplasmic Reticulum Ca2+ - ATPase
- PMCA: Plasma Membrane Ca2+ - ATPase
Mechanism
SERCA lowers intracellular calcium by sequestering calcium ions in the smooth ER whilst PMCA lowers calcium by pumping it out of the cell.
Vasodilators will stimulate SERCA and PMCA via secondary chemical messengers such as cGMP (e.g. nitrous oxide) and cAMP (e.g. prostacyclin) which in turn act by elevating protein kinase A and G (PKA and PKG).
Endothelin-1 is an extremely potent vasoconstrictor and plays an important role in maintaining blood pressure. Its release by the endothelium is stimulated by the following (mainly other vasoconstrictors):
- Angiotensin II
- Antidiuretic hormone (ADH)
- Noradrenaline
- Hypoxia
Prostacyclin and thromboxane A2 are eicosanoids (signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid).