View source for Vasoconstriction

{{short description|Narrowing of blood vessels due to the constriction of smooth muscle cells}}
{{Infobox anatomy
| Name = Vasoconstriction
| Latin =
| Greek =
| Image = {{Multiple image
   | image1 = Cardiovascular system - Vasoconstriction 1 -- Smart-Servier.png
   | width1 = 100
   | image2 = Cardiovascular system - Vasoconstriction 3 -- Smart-Servier.png
   | width2 = 100
   | border = infobox
   | image_gap = 30
}}
| Caption = Schematic depiction of relaxed vessel wall (left) and vasoconstriction (right)
| Width =
| Image2 = Microvessel.jpg
| Caption2 = [[Transmission electron microscopy|Transmission]] [[Micrograph|electron micrograph]] showing vasoconstriction of a [[microvessel]]  by [[pericyte]]s and [[endothelial cell]]s resulting in the deformation of an [[erythrocyte]] (E)
}}

'''Vasoconstriction''' is the narrowing of the [[blood vessel]]s 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 [[antihypotensive agent|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 [[pupillary response|pupil dilation]]. Medications that cause vasoconstriction include: [[antihistamine]]s, [[decongestant]]s, and [[stimulant]]s. Severe vasoconstriction may result in symptoms of [[intermittent claudication]].<ref>{{cite web|url=https://www.drugs.com/pro/medihaler-ergotamine.html|title=Medihaler Ergotamine|website=[[drugs.com]]|access-date=2016-05-20}}</ref>

==General mechanism==
The mechanism that leads to vasoconstriction results from the increased concentration of [[calcium]] (Ca<sup>2+</sup> [[ions]]) within vascular [[smooth muscle cells]].<ref>
{{cite journal
| author1=Michael P. Walsh
| author2=David P. Wilson
| author3=Marija Susnjar
| author4=Enikő Kiss
| author5=Cindy Sutherland
| display-authors=1
| date=2005-08-01<!--Print date and PubMed Central date-->
| orig-date=Published on Journal website 2005-07-26
| title=Thromboxane A<sub>2</sub>-induced contraction of rat caudal arterial smooth muscle involves activation of Ca<sup>2+</sup> entry and Ca<sup>2+</sup>sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697
| journal=Biochem J
| volume=389
| issue=3
| pages=763–774
| doi=10.1042/BJ20050237
| pmc=1180727
| pmid=15823093
| language=en
| quote=These results suggest that U-46619 elicits contraction of rat caudal arterial smooth muscle by activating Ca<sup>2+</sup> entry from the extracellular space, which may or may not involve Ca<sup>2+</sup>-induced Ca<sup>2+</sup> release from the SR (sarcoplasmic reticulum). ... A key step in the contractile response to U-46619 appears to be the entry of extracellular Ca<sup>2+</sup>, since it was abolished by removal of extracellular Ca<sup>2+</sup> (Figure 2A). ... In the rat caudal artery, U-46619-mediated contractile responses have an absolute requirement for Ca<sup>2+</sup>, which enters from the extracellular pool, is independent of intracellular Ca<sup>2+</sup> stores and is blocked by ROK inhibition.
}}
</ref> 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 [[Inositol triphosphate|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 [[phosphorylation|phosphorylating]] the light chain of [[myosin]] to stimulate cross-bridge cycling.<ref>{{cite journal |title=Control of cross-bridge cycling by myosin light chain phosphorylation in mammalian smooth muscle |journal=Acta Physiologica Scandinavica |date=December 1998 |volume=164 |issue=4 |pages=389–400 |doi=10.1046/j.1365-201x.1998.00450.x |pmid=9887963 |last1=Butler |last2=Siegman }}</ref>

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|date=April 2022}}

==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).{{citation needed|date=June 2021}}

Exposure to water causes vasoconstriction near the skin, which in turn causes [[water-immersion wrinkling]].{{citation needed|date=April 2024}}

===Examples===
Examples include [[stimulants]], [[amphetamine]]s, and [[antihistamine]]s. Many are used in medicine to treat [[hypotension]] and as [[topical decongestant]]s. Vasoconstrictors are also used clinically to increase [[blood pressure]] or to reduce local blood flow. [[Local anesthetics and vasoconstrictors|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]].<ref>{{cite journal |author=Yagiela JA |title=Vasoconstrictor agents for local anesthesia |journal=Anesth Prog |volume=42 |issue=3–4 |pages=116–20 |year=1995 |pmid=8934977 |pmc=2148913}}</ref><ref>{{cite journal |last1=Moodley |first1=D. S. |title=Local anaesthetics in dentistry - Part 3: Vasoconstrictors in local anaesthetics |journal=South African Dental Journal |date=May 2017 |volume=72 |issue=4 |pages=176–178 |hdl=10566/3893 |hdl-access=free }}</ref>

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.<ref>{{cite journal |last1=Salerno |first1=Stephen M. |last2=Jackson |first2=Jeffrey L. |last3=Berbano |first3=Elizabeth P. |title=Effect of Oral Pseudoephedrine on Blood Pressure and Heart Rate: A Meta-analysis |journal=Archives of Internal Medicine |date=8 August 2005 |volume=165 |issue=15 |pages=1686–1694 |doi=10.1001/archinte.165.15.1686 |pmid=16087815 }}</ref><ref>{{cite journal |last1=Horak |first1=Friedrich |last2=Zieglmayer |first2=Petra |last3=Zieglmayer |first3=René |last4=Lemell |first4=Patrick |last5=Yao |first5=Ruji |last6=Staudinger |first6=Heribert |last7=Danzig |first7=Melvyn |title=A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber |journal=Annals of Allergy, Asthma & Immunology |date=February 2009 |volume=102 |issue=2 |pages=116–120 |doi=10.1016/s1081-1206(10)60240-2 |pmid=19230461 }}</ref> Examples include:<ref>{{cite book |doi=10.1007/7854_2016_64 |chapter=Pharmacology and Toxicology of N-Benzylphenethylamine ('NBOMe') Hallucinogens |title=Neuropharmacology of New Psychoactive Substances (NPS) |series=Current Topics in Behavioral Neurosciences |date=2017 |last1=Halberstadt |first1=Adam L. |volume=32 |pages=283–311 |pmid=28097528 |isbn=978-3-319-52442-9 }}</ref><ref>{{cite journal |last1=Echeverri |first1=Darío |last2=Montes |first2=Félix R. |last3=Cabrera |first3=Mariana |last4=Galán |first4=Angélica |last5=Prieto |first5=Angélica |title=Caffeine's Vascular Mechanisms of Action |journal=International Journal of Vascular Medicine |date=25 August 2010 |volume=2010 |pages=1–10 |doi=10.1155/2010/834060 |pmid=21188209 |pmc=3003984 |doi-access=free }}</ref><ref>{{Cite journal |last1=Laccourreye |first1=O. |last2=Werner |first2=A. |last3=Giroud |first3=J.-P. |last4=Couloigner |first4=V. |last5=Bonfils |first5=P. |last6=Bondon-Guitton |first6=E. |date=2015 |title=Benefits, limits and danger of ephedrine and pseudoephedrine as nasal decongestants |journal=European Annals of Otorhinolaryngology, Head and Neck Diseases |volume=132 |issue=1 |pages=31–34 |doi=10.1016/j.anorl.2014.11.001 |pmid=25532441 |doi-access=free }}</ref>
{| class="wikitable"
|-
!Vasoconstrictors
|-
|[[25I-NBOMe]]
|-
|[[Amphetamine]]s
|-
|[[Alpha-Methyltryptamine|AMT]]
|-
|[[Antihistamines]]
|-
|[[Caffeine]]
|-
|[[Cocaine]]
|-
|[[2,5-Dimethoxy-4-methylamphetamine|DOM]]
|-
|[[Ergometrine]]
|-
|[[Ergine|LSA]]
|-
|[[Lysergic acid diethylamide|LSD]]
|-
|[[Methylphenidate]]
|-
|[[Mephedrone]]
|-
|[[Naphazoline]]
|-
|[[Nicotine]]<ref>{{Cite journal |last1=Hwang |first1=Kun |last2=Son |first2=Ji Soo |last3=Ryu |first3=Woo Kyung |date=November 2018 |title=Smoking and Flap Survival |journal=Plastic Surgery (Oakville, Ont.) |volume=26 |issue=4 |pages=280–285 |doi=10.1177/2292550317749509 |issn=2292-5503 |pmc=6236508 |pmid=30450347}}</ref>
|-
|[[Oxymetazoline]]
|-
|[[Phenylephrine]]
|-
|[[Propylhexedrine]]
|-
|[[Pseudoephedrine]]
|-
|[[Stimulant]]s
|-
|[[Tetrahydrozoline|Tetrahydrozoline hydrochloride]] (in eye drops)
|-
|[[Xylometazoline]]
|}

===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).{{citation needed|date=June 2021}}

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. [[Adenosine triphosphate|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|date=June 2021}}

{| class="wikitable"
|-
!Vasoconstrictor<ref name=boron/>
!Receptor <br> (↑ = opens. ↓ = closes)<ref name=boron/> <br> <span style="font-size:85%;"> On [[vascular smooth muscle cells]] if not otherwise specified</span>
!Transduction <br> (↑ = increases. ↓ = decreases)<ref name=boron>Unless else specified in box, then ref is: {{cite book |author=Walter F. Boron |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |year= 2005|isbn=1-4160-2328-3 }} Page 479</ref>
|-
| Stretch || ↑[[Stretch-activated ion channel]]s
|rowspan=2| [[depolarization]] -->
* open [[Voltage-dependent calcium channel|VDCC]]s (primarily) --> ↑intracellular Ca<sup>2+</sup>
* ↑Voltage-gated [[sodium channel|Na<sup>+</sup> channel]]s -->
** more depolarization --> open [[Voltage-dependent calcium channel|VDCC]]s --> ↑intracellular Ca<sup>2+</sup>
** ↓[[Sodium-calcium exchanger|Na<sup>+</sup>-Ca<sup>2+</sup> exchanger]] activity --> ↑intracellular Ca<sup>2+</sup>
|-
| [[adenosine triphosphate|ATP]] (intracellular) || ↓[[ATP-sensitive potassium channel|ATP-sensitive K<sup>+</sup> channel]]
|-
| [[adenosine triphosphate|ATP]] (extracellular) || ↑[[P2X receptor]] || ↑Ca<sup>2+</sup>
|-
|[[Neuropeptide Y|NPY]] || [[NPY receptor]]
|| Activation of [[gi alpha subunit|G<sub>i</sub>]] --> ↓[[cyclic adenosine monophosphate|cAMP]] --> ↓[[protein kinase A|PKA]] activity --> ↓[[phosphorylation]] of [[myosin light chain kinase|MLCK]] --> ↑MLCK activity --> ↑phosphorylation of [[myosin light chain|MLC]] (calcium-independent)
|-
| [[adrenergic agonists]] <br> e.g., [[epinephrine]], [[norepinephrine]], and [[dopamine]]|| ↑[[alpha-1 adrenergic receptor|α<sub>1</sub> adrenergic receptor]]
|rowspan=3| Activation of [[gq alpha subunit|G<sub>q</sub>]] --> ↑[[phospholipase C|PLC]] activity --> ↑[[Inositol triphosphate|IP<sub>3</sub>]] and [[diacylglycerol|DAG]] --> activation of [[Inositol triphosphate receptor|IP<sub>3</sub> receptor]] in [[sarcoplasmic reticulum|SR]] --> ↑intracellular Ca<sup>2+</sup>
|-
| [[thromboxane]] || ↑[[thromboxane receptor]]
|-
| [[endothelin]] || ↑[[endothelin receptor]] ET<sub>A</sub>
|-
|rowspan=2| [[angiotensin II]] || ↑[[Angiotensin receptor#AT1|Angiotensin receptor 1]]
|
* On smooth muscle cells: Activation of [[gq alpha subunit|G<sub>q</sub>]] --> ↑[[phospholipase C|PLC]] activity --> ↑[[Inositol triphosphate|IP<sub>3</sub>]] and [[diacylglycerol|DAG]] --> activation of [[Inositol triphosphate receptor|IP<sub>3</sub> receptor]] in [[sarcoplasmic reticulum|SR]] --> ↑intracellular Ca<sup>2+</sup>
* On [[endothelium]]: [[endothelin]] synthesis<ref name=lange6th/>
|-
|  || open [[Voltage-dependent calcium channel|VDCC]]s --> ↑intracellular Ca<sup>2+</sup><ref name=boron2>{{cite book |author=Walter F. Boron |title=Medical Physiology: A Cellular And Molecular Approach |publisher=Elsevier/Saunders |year= 2005|isbn=1-4160-2328-3 }} Page 771</ref>
|-
| [[Asymmetric dimethylarginine]] ||||Reduced production of [[nitric oxide]]
|-
|rowspan=2| [[Vasopressin|Antidiuretic hormone (ADH or Vasopressin)]] || [[Arginine vasopressin receptor 1]] (V1) on smooth muscle cells
| Activation of [[gq alpha subunit|G<sub>q</sub>]] --> ↑[[phospholipase C|PLC]] activity --> ↑[[Inositol triphosphate|IP<sub>3</sub>]] and [[diacylglycerol|DAG]] --> activation of [[Inositol triphosphate receptor|IP<sub>3</sub> receptor]] in [[sarcoplasmic reticulum|SR]] --> ↑intracellular Ca<sup>2+</sup>
|-
| [[Arginine vasopressin receptor]] on endothelium || [[Endothelin]] production<ref name=lange6th/>
|-
|
* Products of [[platelet activation]]<ref name=lange6th>{{cite book |author1=Rod Flower |author2=Humphrey P. Rang |author3=Maureen M. Dale |author4=Ritter, James M. |title=Rang & Dale's pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2007 |isbn=978-0-443-06911-6 }}</ref>
* [[Endotoxin]]<ref name=lange6th/>
* [[Thrombin]]<ref name=lange6th/>
* [[insulin]]<ref name=lange6th/>
* [[Hypoxia (medical)|Hypoxia]]<ref name=lange6th/>
* Low [[shear stress]]<ref name=lange6th/>
| Various receptors on [[endothelium]]<ref name=lange6th/>  || [[Endothelin]] production<ref name=lange6th/>
|}

==Pathology==
Vasoconstriction can be a contributing factor to [[erectile dysfunction]].<ref>Richard Milsten and Julian Slowinski, ''The sexual [[male]]'', bc, main point W.W. Norton Company, New York, London (1999) {{ISBN|0-393-04740-7}}</ref> An increase in blood flow to the penis causes an erection.

Improper vasoconstriction may also play a role in secondary [[hypertension]].{{citation needed|date=April 2022}}

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.<ref>{{cite journal |last1=Swenson |first1=Erik R. |title=Hypoxic Pulmonary Vasoconstriction |journal=High Altitude Medicine & Biology |date=June 2013 |volume=14 |issue=2 |pages=101–110 |doi=10.1089/ham.2013.1010 |pmid=23795729 }}</ref>

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.<ref>{{cite journal |last1=Temprano |first1=Katherine K. |title=A Review of Raynaud's Disease |journal=Missouri Medicine |date=March 2016 |volume=113 |issue=2 |pages=123–126 |pmid=27311222 |pmc=6139949 }}</ref>

==See also==
{{Div col|colwidth=20em}}
* [[Addison's disease]]
* [[Inotrope]]
* [[Hypertension]]
* [[Nitric oxide]]
* [[Pheochromocytoma]]
* [[Shock (circulatory)|Shock]]
* [[Vasodilation]]
* [[Postural orthostatic tachycardia syndrome]]
* [[Hemostasis]]
{{Div col end}}

==References==
{{Reflist}}

==External links==
{{Commons category|Vasoconstrictors}}
* [https://web.archive.org/web/20071228233918/http://www.healthscout.com/ency/1/002338.html Definition of Vasoconstriction on HealthScout]
* {{cite journal |last1=Disdier |first1=Patrick |last2=Granel |first2=Brigitte |last3=Serratrice |first3=Jacques |last4=Constans |first4=Joël |last5=Michon-Pasturel |first5=Ulrique |last6=Hachulla |first6=Eric |last7=Conri |first7=Claude |last8=Devulder |first8=Bernard |last9=Swiader |first9=Laure |last10=Piquet |first10=Philippe |last11=Branchereau |first11=Alain |last12=Jouglard |first12=Jacqueline |last13=Moulin |first13=Guy |last14=Weiller |first14=Pierre-Jean |title=Cannabis Arteritis Revisited: Ten New Case Reports |journal=Angiology |date=January 2001 |volume=52 |issue=1 |pages=1–5 |doi=10.1177/000331970105200101 |pmid=11205926 |s2cid=26030253 }}
* [https://web.archive.org/web/20071209115724/http://www.aegis.com/conferences/Lipo/2003/34.html Are coronary heart disease and peripheral arterial disease associated with tobacco or cannabis consumption]

{{Cardiovascular physiology}}

[[Category:Vasoconstrictors| ]]
[[Category:Cardiovascular physiology]]