Vasoconstriction

Vasoconstriction
Vasoconstriction
	Transmission electron micrograph showing vasoconstriction of a microvessel by pericytes and endothelial cells resulting in the deformation of an erythrocyte (E).
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]

General mechanism

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.

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.

Causes

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).

Examples

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.[3][4]

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.

Examples include:

Vasoconstrictors
25I-NBOMe
Amphetamines
AMT
Antihistamines
Caffeine
Cocaine
DOM
Ergometrine
LSA
LSD
Methylphenidate
Mephedrone
Naphazoline
Oxymetazoline
Phenylephrine
Propylhexedrine
Pseudoephedrine
Stimulants
Tetrahydrozoline hydrochloride (in eye drops)

Endogenous

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).

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.

Vasoconstrictor[5]	Receptor (↑ = opens. ↓ = closes)[5] On vascular smooth muscle cells if not otherwise specified	Transduction (↑ = increases. ↓ = decreases)[5]
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
ATP (extracellular)	↑P2X receptor	↑Ca²⁺
NPY	NPY receptor	Activation of G_i --> ↓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 G_q --> ↑PLC activity --> ↑IP₃ and DAG --> activation of IP₃ receptor in SR --> ↑intracellular Ca²⁺
thromboxane	↑thromboxane receptor
endothelin	↑endothelin receptor ET_A
angiotensin II	↑Angiotensin receptor 1	On smooth muscle cells: Activation of G_q --> ↑PLC activity --> ↑IP₃ and DAG --> activation of IP₃ receptor in SR --> ↑intracellular Ca²⁺ On endothelium: endothelin synthesis[6]
angiotensin II		open VDCCs --> ↑intracellular Ca²⁺[7]
Asymmetric dimethylarginine		Reduced production of nitric oxide
Antidiuretic hormone (ADH or Vasopressin)	Arginine vasopressin receptor 1 (V1) on smooth muscle cells	Activation of G_q --> ↑PLC activity --> ↑IP₃ and DAG --> activation of IP₃ receptor in SR --> ↑intracellular Ca²⁺
Antidiuretic hormone (ADH or Vasopressin)	Arginine vasopressin receptor on endothelium	Endothelin production[6]
Products of platelet activation[6] Endotoxin[6] Thrombin[6] insulin[6] Hypoxia[6] Low shear stress[6]	Various receptors on endothelium[6]	Endothelin production[6]

Pathology

Vasoconstriction can be a contributing factor to erectile dysfunction.[8] An increase in blood flow to the penis causes an erection.

Improper vasoconstriction may also play a role in secondary hypertension.

References

"Medihaler Ergotamine". drugs.com. Retrieved 2016-05-20.
Michael P. Walsh; et al. (2005-08-01) [Published on Journal website 2005-07-26]. "Thromboxane A₂-induced contraction of rat caudal arterial smooth muscle involves activation of Ca²⁺ entry and Ca²⁺sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697". Biochem J. 389 (3): 763–774. doi:10.1042/BJ20050237. PMC 1180727. PMID 15823093. 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.
Yagiela JA (1995). "Vasoconstrictor agents for local anesthesia". Anesth Prog. 42 (3–4): 116–20. PMC 2148913. PMID 8934977.
Moodley, DS (2017). "Local anaesthetics in dentistry-Part 3: Vasoconstrictors in local anaesthetics" (PDF). South African Dental Journal. 72: 176–178.
Unless else specified in box, then ref is: Walter F. Boron (2005). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 479
Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-06911-6.
Walter F. Boron (2005). Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 771
Richard Milsten and Julian Slowinski, The sexual male, bc, main point W.W. Norton Company, New York, London (1999) ISBN 0-393-04740-7

External links

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[1] "Medihaler Ergotamine". drugs.com. Retrieved 2016-05-20.

[2] Michael P. Walsh; et al. (2005-08-01) [Published on Journal website 2005-07-26]. "Thromboxane A₂-induced contraction of rat caudal arterial smooth muscle involves activation of Ca²⁺ entry and Ca²⁺sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697". Biochem J. 389 (3): 763–774. doi:10.1042/BJ20050237. PMC 1180727. PMID 15823093. 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.

[3] Yagiela JA (1995). "Vasoconstrictor agents for local anesthesia". Anesth Prog. 42 (3–4): 116–20. PMC 2148913. PMID 8934977.

[4] Moodley, DS (2017). "Local anaesthetics in dentistry-Part 3: Vasoconstrictors in local anaesthetics" (PDF). South African Dental Journal. 72: 176–178.

[boron-5] Unless else specified in box, then ref is: Walter F. Boron (2005). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 479

[lange6th-6] Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-06911-6.

[boron2-7] Walter F. Boron (2005). Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 771

[8] Richard Milsten and Julian Slowinski, The sexual male, bc, main point W.W. Norton Company, New York, London (1999) ISBN 0-393-04740-7