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Vasodilation refers to the widening of blood vessels[1] resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large veins, large arteries, and smaller arterioles. The process is essentially the opposite of vasoconstriction, which is the narrowing of blood vessels.

When blood vessels dilate, the flow of blood is increased due to a decrease in vascular resistance. Therefore, dilation of arterial blood vessels (mainly the arterioles) causes a decrease in blood pressure. The response may be intrinsic (due to local processes in the surrounding tissue) or extrinsic (due to hormones or the nervous system). Additionally, the response may be localized to a specific organ (depending on the metabolic needs of a particular tissue, as during strenuous exercise), or it may be systemic (seen throughout the entire systemic circulation).

Drugs that cause vasodilation are termed vasodilators.



The primary function of vasodilation is to increase blood flow in the body to tissues that need it most. This is often in response to a localized need of oxygen, but can occur when the tissue in question is not receiving enough glucose or lipids or other nutrients. Localized tissues utilize multiple ways to increase blood flow including releasing vasodilators, primarily adenosine, into the local instersitial fluid which diffuses to capillary beds provoking local vasodilation. Some physiologists have suggested it is the lack of oxygen itself which causes capillary beds to vasodilate by the smooth muscle hypoxia of the vessels in the region. This latter hypothesis is posited due to the presence of precapillary sphincters in capillary beds. Neither of these approaches to the mechanism of vasodilation is mutually exclusive of the other.[2]

Vasodilation and arterial resistance

Vasodilation directly affects the relationship between mean arterial pressure, cardiac output and total peripheral resistance (TPR). Vasodilation occurs in the time phase of cardiac systole while vasoconstriction follows in the opposite time phase of cardiac diastole. Mathematically, cardiac output (blood flow measured in volume per unit time) is computed by multiplying the heart rate (in beats per minute) and the stroke volume (the volume of blood ejected during ventricular systole). TPR depends on several factors, including the length of the vessel, the viscosity of blood (determined by hematocrit) and the diameter of the blood vessel. The latter is the most important variable in determining resistance, with the TPR changing by the fourth power of the radius. An increase in either of these physiological components (cardiac output or TPR) cause a rise in the mean arterial pressure. Vasodilation works to decrease TPR and blood pressure through relaxation of smooth muscle cells in the tunica media layer of large arteries and smaller arterioles.[3]

Vasodilation occurs in superficial blood vessels of warm-blooded animals when their ambient environment is hot; this process diverts the flow of heated blood to the skin of the animal, where heat can be more easily released into the atmosphere. The opposite physiological process is vasoconstriction. These processes are naturally modulated by local paracrine agents from endothelial cells (e.g. nitric oxide, bradykinin, potassium ions and adenosine), as well as an organism's autonomic nervous system and adrenal glands, both of which secrete catecholamines such as norepinephrine and epinephrine, respectively.

Examples and individual mechanisms

Vasodilation is the result of relaxation in smooth muscle surrounding the blood vessels. This relaxation, in turn, relies on removing the stimulus for contraction, which depends on intracellular calcium ion concentrations and, consequently, phosphorylation of the light chain of the contractile protein myosin. Thus, vasodilation mainly works either by lowering intracellular calcium concentration or the dephosphorylation of myosin. This includes stimulation of myosin light chain phosphatase and induction of calcium symporters and antiporters that pump calcium ions out of the intracellular compartment. This is accomplished through reuptake of ions into the sarcoplasmic reticulum via exchangers and expulsion across the plasma membrane.[4] There are three main intracellular stimuli that can result in the vasodilation of blood vessels. The specific mechanisms to accomplish these effects vary from vasodilator to vasodilator.

Hyperpolarization mediated (Calcium channel blocker)Changes in the resting membrane potential of the cell affects the level of intracellular calcium through modulation of voltage sensitive calcium channels in the plasma membrane.adenosine
cAMP mediatedAdrenergic stimulation results in elevated levels of cAMP and protein kinase A, which results in increasing calcium removal from the cytoplasm.prostacyclin
cGMP mediated (Nitrovasodilator)Through stimulation of protein kinase G.nitric oxide

PDE5 inhibitors and potassium channel openers can also have similar results.

Compounds that mediate the above mechanisms may be grouped as endogenous and exogenous.


Vasodilators [5]Receptor
(↑ = opens. ↓ = closes) [5]
On vascular smooth muscle cells if not otherwise specified
(↑ = increases. ↓ = decreases) [5]
EDHF?hyperpolarization → ↓VDCC → ↓intracellular Ca2+
depolarizationvoltage-gated K+ channel
interstitial K+directly
nitric oxideNO receptor on smooth musclecGMP → ↑PKG activity →
  • phosphorylation of MLCK → ↓MLCK activity → dephosphorylation of MLC
  • SERCA → ↓intracellular Ca2+
NO receptor on endotheliumendothelin synthesis [6]
noradrenalineβ-2 adrenergic receptorGs activity → ↑AC activity → ↑cAMP → ↑PKA activity → phosphorylation of MLCK → ↓MLCK activity → dephosphorylation of MLC
histaminehistamine H1 receptor
prostacyclinIP receptor
prostaglandin D2DP receptor
prostaglandin E2EP receptor
VIPVIP receptorGs activity → ↑AC activity → ↑cAMP → ↑PKA activity →
(extracellular) adenosineA1, A2a and A2b adenosine receptorsATP-sensitive K+ channel → hyperpolarization → close VDCC → ↓intracellular Ca2+
  • (extracellular) ATP
  • (extracellular) ADP
P2Y receptoractivate Gq → ↑PLC activity → ↑intracellular Ca2+ → ↑NOS activity → ↑NO → (see nitric oxide)
L-arginineimidazoline and α-2 receptor?Gi → ↓cAMP → activation of Na+/K+-ATPase[7] --> ↓intracellular Na+ → ↑Na+/Ca2+ exchanger activity → ↓intracellular Ca2+
bradykininbradykinin receptor
substance P
niacin (as nicotinic acid only)
platelet activating factor (PAF)
CO2-interstitial pH → ?[8]
interstitial lactic acid(probably)-
muscle work-
various receptors on endotheliumendothelin synthesis [6]

The vasodilating action of activation of beta-2 receptors (such as by noradrenaline) appears to be endothelium-independent.[9]

Sympathetic nervous system vasodilation

Whereas it is recognized that that the sympathetic nervous system plays an expendable role in vasodilation, it is one of the mechanisms by which it can be accomplished. The spinal cord has both vasodilation and vasoconstriction nerves. The neurons that control vascular vasodilation originate in the hypothalmus. Some sympathetic stimulation of arterioles in skeletal muscle is mediated by epinephrine acting on β-adrenergic receptors of arteriolar smooth muscle which would be mediated by cAMP pathways as mentioned above. However, it has been shown that knocking out this sympathetic stimulation plays little to no role in whether skeletal muscle is able to receive sufficient oxygen even at high levels of exertion, so it is believed that this particular method of vasodilation is of little import to human physiology.[10]

In cases of emotional distress, this system may activate, resulting in fainting due to decreased blood pressure from vasodilation, which is referred to as vasovagal syncope.[11]

Other mechanisms of vasodilation

Other suggested vasodilators or vasodilating factors include:

Therapeutic uses

Vasodilators are used to treat conditions such as hypertension, where the patient has an abnormally high blood pressure, as well as angina, congestive heart failure, erectile dysfunction and where maintaining a lower blood pressure reduces the patient's risk of developing other cardiac problems.[3] Flushing may be a physiological response to vasodilators. A phosphodiesterase inhibitor, works to increase blood flow in the penis through vasodilation. It may also be used to treat pulmonary arterial hypertension (PAH).

See also


  1. ^ "Definition of Vasodilation". 27 April 2011. Retrieved 13 January 2012. 
  2. ^ Guyton, Arthur; Hall, John (2006). "Chapter 17: Local and Humoral Control of Blood Flow by the Tissues". In Gruliow, Rebecca (Book). Textbook of Medical Physiology (11th ed.). Philadelphia, Pennsylvania: Elsevier Inc.. pp. 196–197. ISBN 0-7216-0240-1. 
  3. ^ a b CVPharmacology
  4. ^ American Physiological Society
  5. ^ a b c Unless else specified in box, then ref is: Walter F., PhD. Boron. Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3.  Page 479
  6. ^ a b c d e f g Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-06911-5. 
  7. ^ Regulation of Na+-K+-ATPase by cAMP-dependent protein kinase anchored on membrane via its anchoring protein Kinji Kurihara, Nobuo Nakanishi, and Takao Ueha. Departments of 1 Oral Physiology and 2 Biochemistry, School of Dentistry, Meikai University, Sakado, Saitama 350-0283, Japan
  8. ^ Modin A, Björne H, Herulf M, Alving K, Weitzberg E, Lundberg JO (2001). "Nitrite-derived nitric oxide: a possible mediator of 'acidic-metabolic' vasodilation". Acta Physiol. Scand. 171 (1): 9–16. doi:10.1046/j.1365-201x.2001.171001009.x. PMID 11350258. 
  9. ^ Schindler, C.; Dobrev, D.; Grossmann, M.; Francke, K.; Pittrow, D.; Kirch, W. (2004). "Mechanisms of β-adrenergic receptor–mediated venodilation in humans". Clinical Pharmacology & Therapeutics 75: 49–59. doi:10.1016/j.clpt.2003.09.009.  edit
  10. ^ Guyton (2006) pp. 207-208
  11. ^ Guyton (2006) p. 208
  12. ^ Franco-Cereceda A, Rudehill A (August 1989). "Capsaicin-induced vasodilatation of human coronary arteries in vitro is mediated by calcitonin gene-related peptide rather than substance P or neurokinin A". Acta Physiolgica Scandinavica 136 (4): 575–80. PMID 2476911. Retrieved 2012-01-13.