Vasoconstriction

Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in staunching hemorrhage and acute blood loss. When blood vessels constrict, the flow of blood is restricted or decreased, thus, retaining body heat or increasing vascular resistance. Cutaneously, this makes the skin turn paler because less blood reaches the surface, preventing the radiation of heat. On a larger level, vasoconstriction is one mechanism by which the body regulates and maintains mean arterial pressure.

Substances causing vasoconstriction are called vasoconstrictors or vasopressors. 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 used to treat ADHD.

General mechanism

The mechanism that leads to vasoconstriction results from the increased concentration of calcium (Ca²⁺ ions) within vascular smooth muscle cells. 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 pharmokinetic components are more physiologically relevant. Two common stimuli for eliciting smooth muscle contraction is 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.

Once elevated, the intracellular calcium concentration is returned to its basal level 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.

Factors and individual mechanisms

Factors that trigger vasoconstriction can be of exogenous or endogenous original. Ambient temperature is an example of the former. Cutaneous vasoconstriction will occur because of the body's exposure to the severe cold. Examples of endongeous factors include the autonomic nervous system, circulating hormones and intrinsic mechanisms inherent to the vasculature itself (also referred to as the myogenic response).

Exogenous medications

Examples include amphetamines, antihistamines and cocaine. 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.

The routes of administration varies. They may be both systemic and topical. For example, pseudoephedrine is available systemic (i.e. orally ingested tablets like Sudafed), and topical (such as nose sprays like phenylephrine Neo-synephrine, and eye drops for pupil dilation purposes)

Examples include:

Vasoconstrictors
Amphetamines
antihistamines
Cocaine
LSD
LSA
Methylphenidate
Mephedrone
Oxymetazoline
Phenylephrine
Pseudoephedrine
Stimulants
Caffeine
Tetrahydrozoline hydrochloride (in eye drops)
Psilocybin

Endogenous

Vasoconstriction is a procedure of the body that avoids orthostatic hypotension. It is a part of a body negative feed back loop in which the body tries to restore homeostasis.

For example, vasoconstriction is a hypothermic preventative in which the blood vessels constrict and blood must move at a higher pressure to actively avoid 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.

Vasoconstrictor	Receptor (↑ = opens. ↓ = closes) On vascular smooth muscle cells if not otherwise specified	Transduction (↑ = increases. ↓ = decreases)
Stretch	↑Stretch-activated ion channels	depolarization --> open VDCCs (primarily) --> ↑intracellular Ca2+ ↑Voltage-gated Na+ channels --> more depolarization --> open VDCCs --> ↑intracellular Ca2+ ↓Na+-Ca2+ exchanger activity --> ↑intracellular Ca2+
ATP (intracellular)	↓ATP-sensitive K+ channel
muscarinic agonists e.g. acetylcholine	↑muscarinic receptor M2	Activation of Gi --> ↓cAMP --> ↓PKA activity --> ↓phosphorylation of MLCK --> ↑MLCK activity --> ↑phosphorylation of MLC (calcium-independent)
NPY	NPY receptor
adrenergic agonists e.g. norepinephrine	↑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	On smooth muscle cells: Activation of Gq --> ↑PLC activity --> ↑IP3 and DAG --> activation of IP3 receptor in SR --> ↑intracellular Ca2+ On endothelium: endothelin synthesis
		open VDCCs --> ↑intracellular Ca2+
ATP (extracellular)	↑P2X receptor	↑Ca2+
moderately high levels of stress	-	release of adrenergic agonists
Asymmetric dimethylarginine
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
Products of platelet activation Endotoxin Thrombin Epinephrine insulin Hypoxia Low shear stress	Various receptors on endothelium	Endothelin production

Pathology

Vasoconstriction can be a contributing factor to erectile dysfunction. An increase in blood flow to the penis causes an erection.

Improper vasoconstriction may also play a role in secondary hypertension.

See also

• Addison's disease
• Inotrope
• Hypertension
• Nitric oxide
• Pheochromocytoma
• Shock
• Vasodilation
• Postural orthostatic tachycardia syndrome

External links

• Definition of Vasoconstriction on HealthScout
• Cannabis arteritis revisited--ten new case reports
• Are coronary heart disease and peripheral arterial disease associated with tobacco or cannabis consumption
• Vasoconstrictor effects of Cannabis appear to inhibit Migraine (headache) attacks

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