Vasodilator
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A '''vasodilator''' is a drug or chemical that relaxes the [[smooth muscle]] in blood vessels, which causes them to dilate. Dilation of arterial blood vessels (mainly [[arterioles]]) leads to a decrease in blood pressure.
==Function==
Vasodilation directly affects the relationship between [[mean arterial pressure]] and [[cardiac output]] and [[total peripheral resistance]] (TPR). Mathematically, cardiac output is computed by multiplying the [[heart rate]] (in beats/minute) and the [[stroke volume]] (the volume of blood ejected during [[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. An increase in either of these physiological components (cardiac output or TPR) cause a rise in the mean arterial pressure. Vasodilators work to decrease TPR and blood pressure through relaxation of smooth muscle cells in the [[tunica media]] layer of large [[arteries]] and smaller arterioles.<ref>[http://www.cvpharmacology.com/vasodilator/vasodilators.htm CVPharmacology]</ref>
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 into the atmosphere. The opposite physiological process is [[vasoconstriction]]. These processes are naturally modulated by local [[paracrine]] agents from [[endothelial cells]] (e.g [[bradykinin]], [[adenosine]]), as well as an organism's [[Autonomic Nervous System]] and [[adrenal gland]]s, both of which secrete [[catecholamines]] such as [[norepinephrine]] and [[epinephrine]], respectively.
==Examples and individual mechanisms==
Vasodilation is a result of relaxation in [[smooth muscle]] surrounding the blood vessels. This relaxation, in turn, relies on removing the stimulus for contraction, which depends predominately on intracellular calcium ion concentrations and phosphorylation of [[myosin]] light chain (MLC). Thus, vasodilatation mainly works by either by lowering intracellular calcium concentration or dephosphorylation of MLC. This includes stimulation of [[myosin light chain phosphatase]] and induction of calcium [[symporters]] and [[antiporters]] that pump calcium ions out of the intracellular compartment. This is accomplished through retuptake of ions into the [[sarcoplasmic reticulum]] via exchangers and expulsion across the plasma membrane. <ref>[http://advan.physiology.org/cgi/content/full/27/4/201 American Physiological Society]</ref> The specific mechanisms to accomplish these effects varies from vasodilator to vasodilator.
These may be grouped as [[endogenous]] and [[exogenous]].
===Endogenous ===
{| class="wikitable"
!Vasodilators <ref name=boron/>
!Receptor <br/> (↑ = opens. ↓ = closes) <ref name=boron/>
!Transduction <br/> (↑ = increases. ↓ = decreases) <ref name=boron> Unless else specified in box, then ref is: {{cite book |author=Walter F., PhD. Boron |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |location= |year= |pages= |isbn=1-4160-2328-3 |oclc= |doi=}} Page 479</ref>
|-
| [[Endothelium-derived hyperpolarizing factor|EDHF]] || ?
|rowspan=3| [[hyperpolarization]] --> ↓[[Voltage-dependent calcium channel|VDCC]] --> ↓intracellular Ca<sup>2+</sup>
|-
| [[depolarization]] || ↑[[Voltage-gated sodium channel|Voltage-gated K<sup>+</sup> channel]]
|-
| [[Interstitial fluid|interstitial]] [[potassium|K<sup>+</sup>]] || directly
|-
| [[nitric oxide]] || ↑[[NO receptor]] || ↑[[cyclic GMP|cGMP]] --> ↑[[protein kinase g|PKG]] activity -->
* phosphorylation of [[myosin light chain kinase|MLCK]] --> ↓MLCK activity --> dephosphorylation of MLC
* ↑[[SERCA]] --> ↓intracellular Ca<sup>2+</sup>
|-
| [[Beta-2 adrenergic receptor#agonists|β2 adrenergic agonists]] || [[Beta-2 adrenergic receptor|β-2 adrenergic receptor]]
|rowspan=5| ↑[[Gs alpha subunit|G<sub>s</sub>]] activity --> ↑[[adenylate cyclase|AC]] activity --> ↑[[cyclic AMP|cAMP]] --> ↑[[protein kinase A|PKA]] activity --> phosphorylation of [[myosin light chain kinase|MLCK]] --> ↓MLCK activity --> dephosphorylation of MLC
|-
| [[histamine]] || [[Histamine H2 receptor]]
|-
| [[prostacyclin]] || [[IP receptor]]
|-
| [[Prostaglanding D2|Prostaglandin D<sub>2</sub>]] || [[DP receptor|DP receptor]]
|-
| [[Prostaglanding E2|Prostaglandin E<sub>2</sub>]] || [[EP receptor|EP receptor]]
|-
| [[Vasoactive intestinal peptide|VIP]] || [[Vasoactive intestinal peptide receptor|VIP receptor]] || ↑[[Gs alpha subunit|G<sub>s</sub>]] activity --> ↑[[adenylate cyclase|AC]] activity --> ↑[[cyclic AMP|cAMP]] --> ↑[[protein kinase A|PKA]] activity -->
*phosphorylation of [[myosin light chain kinase|MLCK]] --> ↓MLCK activity --> dephosphorylation of MLC
* open [[Calcium-activated potassium channel|Ca<sup>2+</sup>-activated]] and [[voltage-gated potassium channel|voltage-gated K<sup>+</sup>channel ]]s --> hyperpolarization --> close [[Voltage-dependent calcium channel|VDCC]] --> ↓intracellular Ca<sup>2+</sup>
|-
| (extracellular) [[adenosine]] || [[Adenosine A1 receptor|A<sub>1</sub>]], [[Adenosine A2a receptor|A<sub>2a</sub>]] and [[Adenosine A2b receptor|A<sub>2b</sub>]] [[adenosine receptors]] || ↑[[ATP-sensitive K+ channel|ATP-sensitive K<sup>+</sup> channel]] --> hyperpolarization --> close [[voltage-dependent calcium channel|VDCC]] --> ↓intracellular Ca<sup>2+</sup>
|-
|
* (extracellular) [[adenosine triphosphate|ATP]]
* (extracellular) [[adenosine diphosphate|ADP]]
|| ↑[[P2Y receptor]] || activate [[Gq alpha subunit|G<sub>q</sub>]] --> ↑[[phospholipase c|PLC]] activity --> ↑intracellular Ca<sup>2+</sup> --> ↑[[nitric oxide synthase|NOS]] activity --> ↑[[nitric oxide|NO]] --> (see nitric oxide)
|-
| L-[[Arginine]] || [[imidazoline receptor|imidazoline]] and [[alpha-2 adrenergic receptor|α-2 receptor]]? || [[Gi alpha subunit|G<sub>i</sub>]] --> ↓[[cyclic AMP|cAMP]] --> activation of [[Na+/K+-ATPase|Na<sup>+</sup>/K<sup>+</sup>-ATPase]]<ref>[http://ajpcell.physiology.org/cgi/content/full/279/5/C1516 Regulation of Na+-K+-ATPase by cAMP-dependent protein kinase anchored on membrane via its anchoring protein] Kinji Kurihara, Nobuo Nakanishi, and Takao Ueha. Departments of 1 Oral Physiology and 2 Biochemistry, School of Dentistry, Meikai University, Sakado, Saitama 350-0283, Japan</ref> --> ↓intracellular [[sodium|Na<sup>2+</sup>]] --> ↑[[Sodium-calcium exchanger|Na<sup>+</sup>/Ca<sup>2+</sup> exchanger]] activity --> ↓intracellular Ca<sup>2+</sup>
|-
|[[Bradykinin]] || [[Bradykinin receptor]]||
|-
|[[Substance P]] || ||
|-
|[[Niacin]] (nicotinic acid) || ||
|-
| [[Platelet activating factor]] (PAF) || ||
|-
| [[carbon dioxide|CO<sub>2</sub>]] || -
|rowspan=2| ↓[[Interstitial fluid|interstitial]] [[pH]] --> ?<ref name=pH> {{cite journal |author=Modin A, Björne H, Herulf M, Alving K, Weitzberg E, Lundberg JO |title=Nitrite-derived nitric oxide: a possible mediator of 'acidic-metabolic' vasodilation |journal=Acta Physiol. Scand. |volume=171 |issue=1 |pages=9–16 |year=2001 |pmid=11350258| doi = 10.1046/j.1365-201x.2001.171001009.x <!--Retrieved from CrossRef by DOI bot-->}}</ref>
|-
| (probably) [[Interstitial fluid|interstitial]] [[lactic acid]] || -
|-
| muscle work || - ||
*↑vasodilators:
**↑[[adenosine triphosphate|ATP]] consumption --> ↑[[adenosine]]
**↑[[glucose]] usage --> [[carbon dioxide|CO<sub>2</sub>]]
**↑[[Interstitial fluid|interstitial]] [[sodium|K<sup>+</sup>]]
**↑(extracellular) [[adenosine triphosphate|ATP]]
**↑(extracellular) [[adenosine diphosphate|ADP]]
**↑[[Interstitial fluid|interstitial]] [[sodium|K<sup>+</sup>]]
*↓[[vasoconstrictors]]:
**↑[[adenosine triphosphate|ATP]] consumption --> ↓ ATP (intracellular)
**↓[[oxygen]] --> ↓[[oxidative phosphorylation]] --> ↓ ATP (intracellular)
|}
===Exogenous vasodilators===
* Absence of high levels of [[environmental noise]]
* Absence of [[over-illumination|high levels of illumination]]
* Adenocard - Adenosine agonist, primarily used as an anti-[[arrhythmia|arrhythmic]].
* [[Alpha blocker]]s (block the [[vasoconstricting]] effect of [[adrenaline]]).
* [[Amyl nitrite]] and other nitrites are often used recreationally as a vasodilator, causing lightheadedness and a euphoric feeling.
* [[Atrial natriuretic peptide]] (ANP) - a weak vasodilator.
* [[Ethanol]]
* Histamine-inducers
** [[Complement system|Complement]] proteins C3a, C4a and C5a work by triggering histamine release from [[mast cell]]s and [[basophil granulocyte]]s.
* Nitric oxide inducers
** [[Glyceryl trinitrate]] (commonly known as [[Nitroglycerin]])
** [[Isosorbide mononitrate]] & [[Isosorbide dinitrate]]
** [[PETN|Pentaerythritol Tetranitrate]] (PETN)
** [[Sodium nitroprusside]]
** [[PDE5 inhibitor]]s: these agents indirectly increase the effects of nitric oxide
*** [[Sildenafil]] (Viagra)
*** [[Tadalafil]]
*** [[Vardenafil]]
* [[Tetrahydrocannabinol]] (THC) - the major active chemical in [[Medical cannabis|marijuana]]. Its mild vasodilating effects redden the eyes of [[cannabis (drug)|cannabis]] smokers.
* [[Theobromine]].
* [[Papaverine]] an alkaloid found in the opium poppy [[papaver somniferum]]
====Therapeutic uses====
Vasodilators are used to treat conditions such as [[hypertension]], where the patient has an abnormally high blood pressure, as well as angina and [[congestive heart failure]], where maintaining a lower blood pressure reduces the patient's risk of developing other cardiac problems.<ref>[http://www.cvpharmacology.com/vasodilator/vasodilators.htm CVPharmacology]</ref>
[[Flushing (physiology)|Flushing]] may be a physiological response to vasodilators.
==References==
{{reflist}}
{{Major Drug Groups}}
{{Vasodilators used in cardiac diseases}}
{{Peripheral vasodilators}}
{{Cardiovascular physiology}}
{{pharma-stub}}
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