Vasoconstriction | |
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Identifiers | |
MeSH | D014661 |
Anatomical terminology |
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in controlling hemorrhage and reducing acute blood loss. When blood vessels constrict, the flow of blood is restricted or decreased, thus retaining body heat or increasing vascular resistance. This makes the skin turn paler because less blood reaches the surface, reducing the radiation of heat. On a larger level, vasoconstriction is one mechanism by which the body regulates and maintains mean arterial pressure.
Medications causing vasoconstriction, also known as vasoconstrictors, are one type of medicine used to raise blood pressure. Generalized vasoconstriction usually results in an increase in systemic blood pressure, but it may also occur in specific tissues, causing a localized reduction in blood flow. The extent of vasoconstriction may be slight or severe depending on the substance or circumstance. Many vasoconstrictors also cause pupil dilation. Medications that cause vasoconstriction include: antihistamines, decongestants, and stimulants. Severe vasoconstriction may result in symptoms of intermittent claudication. [1]
The mechanism that leads to vasoconstriction results from the increased concentration of calcium (Ca2+ ions) within vascular smooth muscle cells. [2] However, the specific mechanisms for generating an increased intracellular concentration of calcium depends on the vasoconstrictor. Smooth muscle cells are capable of generating action potentials, but this mechanism is rarely utilized for contraction in the vasculature. Hormonal or pharmacokinetic components are more physiologically relevant. Two common stimuli for eliciting smooth muscle contraction are circulating epinephrine and activation of the sympathetic nervous system (through release of norepinephrine) that directly innervates the muscle. These compounds interact with cell surface adrenergic receptors. Such stimuli result in a signal transduction cascade that leads to increased intracellular calcium from the sarcoplasmic reticulum through IP3-mediated calcium release, as well as enhanced calcium entry across the sarcolemma through calcium channels. The rise in intracellular calcium complexes with calmodulin, which in turn activates myosin light-chain kinase. This enzyme is responsible for phosphorylating the light chain of myosin to stimulate cross-bridge cycling. [3]
Once elevated, the intracellular calcium concentration is returned to its normal concentration through a variety of protein pumps and calcium exchangers located on the plasma membrane and sarcoplasmic reticulum. This reduction in calcium removes the stimulus necessary for contraction, allowing for a return to baseline.[ citation needed ]
Factors that trigger vasoconstriction can be exogenous or endogenous in origin. Ambient temperature is an example of exogenous vasoconstriction. Cutaneous vasoconstriction will occur because of the body's exposure to the severe cold. Examples of endogenous factors include the autonomic nervous system, circulating hormones, and intrinsic mechanisms inherent to the vasculature itself (also referred to as the myogenic response).[ citation needed ]
Exposure to water causes vasoconstriction near the skin, which in turn causes water-immersion wrinkling.[ citation needed ]
Examples include stimulants, amphetamines, and antihistamines. Many are used in medicine to treat hypotension and as topical decongestants. Vasoconstrictors are also used clinically to increase blood pressure or to reduce local blood flow. Vasoconstrictors mixed with local anesthetics are used to increase the duration of local anesthesia by constricting the blood vessels, thereby safely concentrating the anesthetic agent for an extended duration, as well as reducing hemorrhage. [4] [5]
The routes of administration vary. They may be both systemic and topical. For example, pseudoephedrine is taken orally and phenylephrine is topically applied to the nasal passages or eyes. [6] [7] Examples include: [8] [9] [10]
Vasoconstriction is a procedure of the body that averts orthostatic hypotension. It is part of a body negative feedback loop in which the body tries to restore homeostasis (maintain constant internal environment).[ citation needed ]
For example, vasoconstriction is a hypothermic preventative in which the blood vessels constrict and blood must move at a higher pressure to actively prevent a hypoxic reaction. ATP is used as a form of energy to increase this pressure to heat the body. Once homeostasis is restored, the blood pressure and ATP production regulates. Vasoconstriction also occurs in superficial blood vessels of warm-blooded animals when their ambient environment is cold; this process diverts the flow of heated blood to the center of the animal, preventing the loss of heat.[ citation needed ]
Vasoconstrictor [12] | Receptor (↑ = opens. ↓ = closes) [12] On vascular smooth muscle cells if not otherwise specified | Transduction (↑ = increases. ↓ = decreases) [12] |
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Stretch | ↑Stretch-activated ion channels | depolarization -->
|
ATP (intracellular) | ↓ATP-sensitive K+ channel | |
ATP (extracellular) | ↑P2X receptor | ↑Ca2+ |
NPY | NPY receptor | Activation of Gi --> ↓cAMP --> ↓PKA activity --> ↓phosphorylation of MLCK --> ↑MLCK activity --> ↑phosphorylation of MLC (calcium-independent) |
adrenergic agonists e.g., epinephrine, norepinephrine, and dopamine | ↑α1 adrenergic receptor | Activation of Gq --> ↑PLC activity --> ↑IP3 and DAG --> activation of IP3 receptor in SR --> ↑intracellular Ca2+ |
thromboxane | ↑thromboxane receptor | |
endothelin | ↑endothelin receptor ETA | |
angiotensin II | ↑Angiotensin receptor 1 |
|
open VDCCs --> ↑intracellular Ca2+ [14] | ||
Asymmetric dimethylarginine | Reduced production of nitric oxide | |
Antidiuretic hormone (ADH or Vasopressin) | Arginine vasopressin receptor 1 (V1) on smooth muscle cells | Activation of Gq --> ↑PLC activity --> ↑IP3 and DAG --> activation of IP3 receptor in SR --> ↑intracellular Ca2+ |
Arginine vasopressin receptor on endothelium | Endothelin production [13] | |
Various receptors on endothelium [13] | Endothelin production [13] |
Vasoconstriction can be a contributing factor to erectile dysfunction. [15] An increase in blood flow to the penis causes an erection.
Improper vasoconstriction may also play a role in secondary hypertension.[ citation needed ]
To summarize, vasoconstriction is a physiological process that involves the narrowing of blood vessels, particularly arteries and arterioles, resulting in a reduction of blood flow to specific tissues or organs. This phenomenon is primarily regulated by the contraction of smooth muscle cells within the vessel walls. Several factors contribute to vasoconstriction, including the release of vasoconstrictor substances such as endothelin and angiotensin II, both of which play crucial roles in the modulation of vascular tone. [16]
Additionally, sympathetic nervous system activation, triggered by stress or other stimuli, prompts the release of norepinephrine, a neurotransmitter that induces vasoconstriction by binding to alpha-adrenergic receptors on smooth muscle cells. The narrowing of blood vessels leads to an increase in peripheral resistance, thereby elevating blood pressure. While vasoconstriction is a normal and essential regulatory mechanism for maintaining blood pressure and redistributing blood flow during various physiological processes, its dysregulation can contribute to pathological conditions. Chronic vasoconstriction is associated with hypertension, a major risk factor for cardiovascular diseases such as heart attack and stroke. Moreover, impaired blood flow resulting from abnormal vasoconstriction may contribute to tissue ischemia, which can be observed in conditions like Raynaud's disease. Understanding the pathology of vasoconstriction is crucial for developing targeted therapeutic strategies to manage conditions associated with abnormal vascular tone. [17]
Blood vessels are the structures of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away from the tissues. Blood vessels are typically needed to sustain life, because all of the body's tissues rely on their functionality.
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, beta-2 (β2) agonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example.
Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as medications to decrease blood pressure in patients with hypertension. CCBs are particularly effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are also frequently used to alter heart rate, to prevent peripheral and cerebral vasospasm, and to reduce chest pain caused by angina pectoris.
Smoothmuscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non-striated, so-called because it has no sarcomeres and therefore no striations. It can be divided into two subgroups, single-unit and multi-unit smooth muscle. Within single-unit muscle, the whole bundle or sheet of smooth muscle cells contracts as a syncytium.
The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are kept relatively constant, with the concentration of calcium ions within a cell being 10,000 times smaller than the concentration of calcium ions outside the cell. This means that small increases in calcium ions within the cell are easily detected and can bring about important cellular changes (the calcium is said to be a second messenger). Calcium is used to make calcium carbonate (found in chalk) and calcium phosphate, two compounds that the body uses to make teeth and bones. This means that too much calcium within the cells can lead to hardening (calcification) of certain intracellular structures, including the mitochondria, leading to cell death. Therefore, it is vital that calcium ion levels are controlled tightly, and can be released into the cell when necessary and then removed from the cell.
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel walls are composed of endothelial tissue and a basal membrane lining the lumen of the vessel, concentric smooth muscle layers on top of endothelial tissue, and an adventitia over the smooth muscle layers. Relaxation of the smooth muscle layer allows the blood vessel to dilate, as it is held in a semi-constricted state by sympathetic nervous system activity. Vasodilation is the opposite of vasoconstriction, which is the narrowing of blood vessels.
The Frank–Starling law of the heart represents the relationship between stroke volume and end diastolic volume. The law states that the stroke volume of the heart increases in response to an increase in the volume of blood in the ventricles, before contraction, when all other factors remain constant. As a larger volume of blood flows into the ventricle, the blood stretches cardiac muscle, leading to an increase in the force of contraction. The Frank-Starling mechanism allows the cardiac output to be synchronized with the venous return, arterial blood supply and humoral length, without depending upon external regulation to make alterations. The physiological importance of the mechanism lies mainly in maintaining left and right ventricular output equality.
In haemodynamics, the body must respond to physical activities, external temperature, and other factors by homeostatically adjusting its blood flow to deliver nutrients such as oxygen and glucose to stressed tissues and allow them to function. Haemodynamic response (HR) allows the rapid delivery of blood to active neuronal tissues. The brain consumes large amounts of energy but does not have a reservoir of stored energy substrates. Since higher processes in the brain occur almost constantly, cerebral blood flow is essential for the maintenance of neurons, astrocytes, and other cells of the brain. This coupling between neuronal activity and blood flow is also referred to as neurovascular coupling.
Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as when holding something heavy in the same position. The termination of muscle contraction is followed by muscle relaxation, which is a return of the muscle fibers to their low tension-generating state.
Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among numerous others, is a medication used as a decongestant for uncomplicated nasal congestion, used to dilate the pupil, used to increase blood pressure, and used to relieve hemorrhoids. It can be taken by mouth, as a nasal spray, given by injection into a vein or muscle, applied to the skin, or as a rectal suppository.
The myometrium is the middle layer of the uterine wall, consisting mainly of uterine smooth muscle cells but also of supporting stromal and vascular tissue. Its main function is to induce uterine contractions.
Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins. Ca2+ can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.
Myosin light-chain kinase also known as MYLK or MLCK is a serine/threonine-specific protein kinase that phosphorylates a specific myosin light chain, namely, the regulatory light chain of myosin II.
There are at least four known endothelin receptors, ETA, ETB1, ETB2 and ETC, all of which are G protein-coupled receptors whose activation result in elevation of intracellular-free calcium, which constricts the smooth muscles of the blood vessels, raising blood pressure, or relaxes the smooth muscles of the blood vessels, lowering blood pressure, among other functions.
Amrinone, also known as inamrinone, and sold as Inocor, is a pyridine phosphodiesterase 3 inhibitor. It is a drug that may improve the prognosis in patients with congestive heart failure. Amrinone has been shown to increase the contractions initiated in the heart by high-gain calcium induced calcium release (CICR). The positive inotropic effect of amrinone is mediated by the selective enhancement of high-gain CICR, which contributes to the contraction of myocytes by phosphorylation through cAMP dependent protein kinase A (PKA) and Ca2+ calmodulin kinase pathways.
The myogenic mechanism is how arteries and arterioles react to an increase or decrease of blood pressure to keep the blood flow constant within the blood vessel. Myogenic response refers to a contraction initiated by the myocyte itself instead of an outside occurrence or stimulus such as nerve innervation. Most often observed in smaller resistance arteries, this 'basal' myogenic tone may be useful in the regulation of organ blood flow and peripheral resistance, as it positions a vessel in a preconstricted state that allows other factors to induce additional constriction or dilation to increase or decrease blood flow.
Transient receptor potential cation channel, subfamily C, member 6 or Transient receptor potential canonical 6, also known as TRPC6, is a protein encoded in the human by the TRPC6 gene. TRPC6 is a transient receptor potential channel of the classical TRPC subfamily.
Vasomotion is the spontaneous oscillation in tone of blood vessel walls, independent of heart beat, innervation or respiration. While vasomotion was first observed by Thomas Wharton Jones in 1852, the complete mechanisms responsible for its generation and its physiological importance remain to be elucidated. However, several hypotheses have been put forth.
Cerebral vasospasm is the prolonged, intense vasoconstriction of the larger conducting arteries in the subarachnoid space which is initially surrounded by a clot.
Cardiac excitation-contraction coupling (CardiacEC coupling) describes the series of events, from the production of an electrical impulse (action potential) to the contraction of muscles in the heart. This process is of vital importance as it allows for the heart to beat in a controlled manner, without the need for conscious input. EC coupling results in the sequential contraction of the heart muscles that allows blood to be pumped, first to the lungs (pulmonary circulation) and then around the rest of the body (systemic circulation) at a rate between 60 and 100 beats every minute, when the body is at rest. This rate can be altered, however, by nerves that work to either increase heart rate (sympathetic nerves) or decrease it (parasympathetic nerves), as the body's oxygen demands change. Ultimately, muscle contraction revolves around a charged atom (ion), calcium (Ca2+), which is responsible for converting the electrical energy of the action potential into mechanical energy (contraction) of the muscle. This is achieved in a region of the muscle cell, called the transverse tubule during a process known as calcium induced calcium release.
These results suggest that U-46619 elicits contraction of rat caudal arterial smooth muscle by activating Ca2+ entry from the extracellular space, which may or may not involve Ca2+-induced Ca2+ release from the SR (sarcoplasmic reticulum). ... A key step in the contractile response to U-46619 appears to be the entry of extracellular Ca2+, since it was abolished by removal of extracellular Ca2+ (Figure 2A). ... In the rat caudal artery, U-46619-mediated contractile responses have an absolute requirement for Ca2+, which enters from the extracellular pool, is independent of intracellular Ca2+ stores and is blocked by ROK inhibition.