Vasodilator 56149 225274301 2008-07-12T20:48:53Z RockMFR 2362410 cleanup 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/> (&uarr; = opens. &darr; = closes) <ref name=boron/> !Transduction <br/> (&uarr; = increases. &darr; = 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]] --> &darr;[[Voltage-dependent calcium channel|VDCC]] --> &darr;intracellular Ca<sup>2+</sup> |- | [[depolarization]] || &uarr;[[Voltage-gated sodium channel|Voltage-gated K<sup>+</sup> channel]] |- | [[Interstitial fluid|interstitial]] [[potassium|K<sup>+</sup>]] || directly |- | [[nitric oxide]] || &uarr;[[NO receptor]] || &uarr;[[cyclic GMP|cGMP]] --> &uarr;[[protein kinase g|PKG]] activity --> * phosphorylation of [[myosin light chain kinase|MLCK]] --> &darr;MLCK activity --> dephosphorylation of MLC * &uarr;[[SERCA]] --> &darr;intracellular Ca<sup>2+</sup> |- | [[Beta-2 adrenergic receptor#agonists|β2 adrenergic agonists]] || [[Beta-2 adrenergic receptor|β-2 adrenergic receptor]] |rowspan=5| &uarr;[[Gs alpha subunit|G<sub>s</sub>]] activity --> &uarr;[[adenylate cyclase|AC]] activity --> &uarr;[[cyclic AMP|cAMP]] --> &uarr;[[protein kinase A|PKA]] activity --> phosphorylation of [[myosin light chain kinase|MLCK]] --> &darr;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]] || &uarr;[[Gs alpha subunit|G<sub>s</sub>]] activity --> &uarr;[[adenylate cyclase|AC]] activity --> &uarr;[[cyclic AMP|cAMP]] --> &uarr;[[protein kinase A|PKA]] activity --> *phosphorylation of [[myosin light chain kinase|MLCK]] --> &darr;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]] --> &darr;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]] || &uarr;[[ATP-sensitive K+ channel|ATP-sensitive K<sup>+</sup> channel]] --> hyperpolarization --> close [[voltage-dependent calcium channel|VDCC]] --> &darr;intracellular Ca<sup>2+</sup> |- | * (extracellular) [[adenosine triphosphate|ATP]] * (extracellular) [[adenosine diphosphate|ADP]] || &uarr;[[P2Y receptor]] || activate [[Gq alpha subunit|G<sub>q</sub>]] --> &uarr;[[phospholipase c|PLC]] activity --> &uarr;intracellular Ca<sup>2+</sup> --> &uarr;[[nitric oxide synthase|NOS]] activity --> &uarr;[[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>]] --> &darr;[[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> --> &darr;intracellular [[sodium|Na<sup>2+</sup>]] --> &uarr;[[Sodium-calcium exchanger|Na<sup>+</sup>/Ca<sup>2+</sup> exchanger]] activity --> &darr;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| &darr;[[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 || - || *&uarr;vasodilators: **&uarr;[[adenosine triphosphate|ATP]] consumption --> &uarr;[[adenosine]] **&uarr;[[glucose]] usage --> [[carbon dioxide|CO<sub>2</sub>]] **&uarr;[[Interstitial fluid|interstitial]] [[sodium|K<sup>+</sup>]] **&uarr;(extracellular) [[adenosine triphosphate|ATP]] **&uarr;(extracellular) [[adenosine diphosphate|ADP]] **&uarr;[[Interstitial fluid|interstitial]] [[sodium|K<sup>+</sup>]] *&darr;[[vasoconstrictors]]: **&uarr;[[adenosine triphosphate|ATP]] consumption --> &darr; ATP (intracellular) **&darr;[[oxygen]] --> &darr;[[oxidative phosphorylation]] --> &darr; 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}} [[Category:Vasodilators| ]] [[ca:Vasodilatació]] [[de:Vasodilatation]] [[es:Vasodilatación]] [[fr:Vasodilatateur]] [[hr:Vazodilatatori]] [[nl:Vasodilatatie]] [[ja:血管拡張薬]] [[no:Vasodilator]] [[pl:Wazodilatacja]] [[pt:Vasodilatação]] [[sr:Вазодилатација]] [[tr:Vazodilatör]] [[uk:Судинорозширювальні речовини]] [[zh:血管舒張]]