Vasodilation

Vasodilation (or vasodilatation) refers to the widening of blood vessels.[1] It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is 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) decreases blood pressure. The response may be intrinsic (due to local processes in the surrounding tissue) or extrinsic (due to hormones or the nervous system). In addition, 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.

Function

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 interstitial fluid, which diffuses to capillary beds, provoking local vasodilation.[2][3] Some physiologists have suggested that it is the lack of oxygen itself that 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.[4]

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, whereas vasoconstriction follows in the opposite time phase of cardiac diastole. 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) causes 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.[5]

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 to 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 is tightly linked with phosphorylation of the light chain of the contractile protein myosin. Thus, vasodilation works mainly either by lowering intracellular calcium concentration or by dephosphorylation (really substitution of ATP for ADP) of myosin. Dephosphorylation by myosin light-chain phosphatase and induction of calcium symporters and antiporters that pump calcium ions out of the intracellular compartment both contribute to smooth muscle cell relaxation and therefore vasodilation. This is accomplished through reuptake of ions into the sarcoplasmic reticulum via exchangers and expulsion across the plasma membrane.[6] 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.

Class Description Example
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-mediated Adrenergic 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.

Endogenous

Vasodilators [7] Receptor
(↑ = opens. ↓ = closes) [7]
On vascular smooth muscle cells if not otherwise specified		 Transduction
(↑ = increases. ↓ = decreases) [7]
EDHF ? hyperpolarization → ↓VDCC → ↓intracellular Ca2+
PKG activity →
  • phosphorylation of MLCK → ↓MLCK activity → dephosphorylation of MLC
  • ↑SERCA → ↓intracellular Ca2+
NO receptor on endothelium ↓endothelin synthesis [8]
epinephrine (adrenaline) β-2 adrenergic receptor ↑Gs activity → ↑AC activity → ↑cAMP → ↑PKA activity → phosphorylation of MLCK → ↓MLCK activity → dephosphorylation of MLC
histamine histamine H2 receptor
prostacyclin IP receptor
prostaglandin D2 DP receptor
prostaglandin E2 EP receptor
VIP VIP receptor ↑Gs activity → ↑AC activity → ↑cAMP → ↑PKA activity →
(extracellular) adenosine A1, A2a and A2b adenosine receptors ↑ATP-sensitive K+ channel → hyperpolarization → close VDCC → ↓intracellular Ca2+
  • (extracellular) ATP
  • (extracellular) ADP
 ↑P2Y receptor activate Gq → ↑PLC activity → ↑intracellular Ca2+ → ↑NOS activity → ↑NO → (see nitric oxide)
L-arginine imidazoline and α-2 receptor? Gi → ↓cAMP → activation of Na+/K+-ATPase[9] → ↓intracellular Na+ → ↑Na+/Ca2+ exchanger activity → ↓intracellular Ca2+
bradykinin bradykinin receptor
substance P
niacin (as nicotinic acid only)
platelet-activating factor (PAF)
CO2 - ↓interstitial pH → ?[10]
interstitial lactic acid(probably) -
muscle work -
various receptors on endothelium ↓endothelin synthesis [8]

The vasodilating action of activation of beta-2 receptors (such as by noradrenaline) appears to be endothelium-independent.[11]

Sympathetic nervous system vasodilation

Although it is recognized that the sympathetic nervous system plays an expendable role in vasodilation, it is only one of the mechanisms by which vasodilation can be accomplished. The spinal cord has both vasodilation and vasoconstriction nerves. The neurons that control vascular vasodilation originate in the hypothalamus. 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 discussed above. However, it has been shown that knocking out this sympathetic stimulation plays little or 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 importance to human physiology.[12]

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.[13]

Cold-induced vasodilation

Cold-induced vasodilation (CIVD) occurs after cold exposure, possibly to reduce the risk of injury. It can take place in several locations in the human body but is observed most often in the extremities. The fingers are especially common because they are exposed most often.

When the fingers are exposed to cold, vasoconstriction occurs first to reduce heat loss, resulting in strong cooling of the fingers. Approximately five to ten minutes after the start of the cold exposure of the hand, the blood vessels in the finger tips will suddenly vasodilate. This is probably caused by a sudden decrease in the release of neurotransmitters from the sympathetic nerves to the muscular coat of the arteriovenous anastomoses due to local cold. The CIVD increases blood flow and subsequently the temperature of the fingers. This can be painful and is sometimes known as the 'hot aches' which can be painful enough to bring on vomiting.

A new phase of vasoconstriction follows the vasodilation, after which the process repeats itself. This is called the Hunting reaction. Experiments have shown that three other vascular responses to immersion of the finger in cold water are possible: a continuous state of vasoconstriction; slow, steady, and continuous rewarming; and a proportional control form in which the blood vessel diameter remains constant after an initial phase of vasoconstriction. However, the vast majority of responses can be classified as the Hunting reaction.[14]

Other mechanisms of vasodilation

Other suggested vasodilators or vasodilating factors include:

Therapeutic uses

Vasodilators are used to treat conditions such as hypertension, wherein the patient has an abnormally high blood pressure, as well as angina, congestive heart failure, and erectile dysfunction, and where maintaining a lower blood pressure reduces the patient's risk of developing other cardiac problems.[5] Flushing may be a physiological response to vasodilators. Some phosphodiesterase inhibitors such as sildenafil, vardenafil and tadalafil, work to increase blood flow in the penis through vasodilation. They may also be used to treat pulmonary arterial hypertension (PAH).

See also

References

  1. ↑ "Definition of Vasodilation". MedicineNet.com. 27 April 2011. Retrieved 13 January 2012.
  2. ↑ Costa, F; Biaggioni, I (May 1998). "Role of nitric oxide in adenosine-induced vasodilation in humans.". Hypertension 31 (5): 1061–4. doi:10.1161/01.HYP.31.5.1061. PMID 9576114.
  3. ↑ Sato, A; Terata, K; Miura, H; Toyama, K; Loberiza FR, Jr; Hatoum, OA; Saito, T; Sakuma, I; Gutterman, DD (April 2005). "Mechanism of vasodilation to adenosine in coronary arterioles from patients with heart disease". American Journal of Physiology. Heart and Circulatory Physiology 288 (4): H1633–40. doi:10.1152/ajpheart.00575.2004. PMID 15772334. Cite uses deprecated parameter |coauthors= (help)
  4. ↑ Guyton, Arthur; Hall, John (2006). "Chapter 17: Local and Humoral Control of Blood Flow by the Tissues". In Gruliow, Rebecca. Textbook of Medical Physiology (Book) (11th ed.). Philadelphia, Pennsylvania: Elsevier Inc. pp. 196–197. ISBN 0-7216-0240-1.
  5. 1 2 Klablunde, Richard E. (2008-04-29). "Therapeutic Uses of Vasodilators". CVPharmacology. Retrieved 2013-12-03.
  6. ↑ Webb, RC (December 2003). "Smooth muscle contraction and relaxation". Advances in physiology education 27 (1–4): 201–6. doi:10.1152/advan.00025.2003. PMID 14627618.
  7. 1 2 3 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
  8. 1 2 3 4 5 6 Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-06911-5.
  9. ↑ Kurihara, Kinji; Nakanishi, Nobuo; Ueha, Takao (1 November 2000). "Regulation of Na+-K+-ATPase by cAMP-dependent protein kinase anchored on membrane via its anchoring protein". American Journal of Physiology. Cell Physiology 279 (5): C1516–C1527. PMID 11029299.
  10. ↑ 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.
  11. ↑ Schindler, C; Dobrev, D; Grossmann, M; Francke, K; Pittrow, D; Kirch, W (January 2004). "Mechanisms of beta-adrenergic receptor-mediated venodilation in humans". Clinical pharmacology and therapeutics 75 (1): 49–59. doi:10.1016/j.clpt.2003.09.009. PMID 14749691.
  12. ↑ Guyton (2006) pp. 207-208
  13. ↑ Guyton (2006) p. 208
  14. ↑ Daanen, H. A. M. (2003). "Finger cold-induced vasodilation: a review". European Journal of Applied Physiology 89 (5): 411–426. doi:10.1007/s00421-003-0818-2. PMID 12712346.
  15. ↑ 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. doi:10.1111/j.1748-1716.1989.tb08704.x. PMID 2476911.
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