出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/01 05:18:38」(JST)
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. In essence, 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.
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 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.
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.
| Vasodilators [7] | Receptor (↑ = opens. ↓ = closes) [7] |
Transduction (↑ = increases. ↓ = decreases) [7] |
|---|---|---|
| EDHF | ? | hyperpolarization → ↓VDCC → ↓intracellular Ca2+ |
PKG activity →
|
||
| 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+ |
|
↑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]
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 (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]
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Other suggested vasodilators or vasodilating factors include:
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. A phosphodiesterase inhibitor, works to increase blood flow in the penis through vasodilation. It may also be used to treat pulmonary arterial hypertension (PAH).
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| リンク元 | 「vasodepressive」「血管抑制性」 |