A vasodilator is a drug or chemical that relaxes the smooth muscle in blood vessels, which causes them to dilate. Smooth muscle is a type of non- Striated muscle, found within the Tunica media layer of large and small Arteries and Veins, the bladder Dilation of arterial blood vessels (mainly arterioles) leads to a decrease in blood pressure. An arteriole is a small diameter Blood vessel that extends and branches out from an Artery and leads to capillaries.
Contents |
Function
Vasodilation directly affects the relationship between mean arterial pressure and cardiac output and total peripheral resistance (TPR). The mean arterial pressure ( MAP) is a term used in medicine to describe a notional average Blood pressure in an individual Cardiac output (Q is the volume of blood being pumped by the Heart, in particular by a ventricle in a minute Total peripheral resistance (TPR is the sum of the resistance of all peripheral vasculature in the systemic circulation Mathematically, cardiac output is computed by multiplying the heart rate (in beats/minute) and the stroke volume (the volume of blood ejected during systole). Measuring heart rate The Pulse rate (which in most people is identical to the heart rate can be measured at any point on the body where an Artery 's pulsation Stroke volume (SV is the volume of Blood pumped by the right/ Left ventricle of the heart in one contraction. 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 hematocrit ( Ht or HCT) or packed cell volume ( PCV) or erythrocyte volume fraction (EVF is the proportion of Blood 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. The tunica media (or just media) ( middle coat) is the middle layer of an Artery or Vein. Arteries are Blood vessels that carry blood away from the Heart. [1]
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. Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels particularly the large Arteries, Arterioles These processes are naturally modulated by local paracrine agents from endothelial cells (e. Paracrine signaling is a form of Cell signaling in which the target cell is near (" Para " = near the signal-releasing cell The endothelium is the thin layer of cells that line the interior surface of Blood vessels forming an interface between circulating Blood in the g bradykinin, adenosine), as well as an organism's Autonomic Nervous System and adrenal glands, both of which secrete catecholamines such as norepinephrine and epinephrine, respectively. Bradykinin is a Peptide that causes blood vessels to enlarge (dilate and therefore causes blood pressure to lower Adenosine is a Nucleoside composed of a Molecule of Adenine attached to a Ribose sugar molecule ( Ribofuranose) moiety via a β-N9- &trade The autonomic nervous system ( ANS) (or visceral nervous system) is the part of the Peripheral nervous system that acts as a Control In Mammals the adrenal glands (also known as suprarenal glands) are the triangle-shaped Endocrine glands that sit on top of the Kidneys their Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a
Examples and individual mechanisms
Vasodilation is a result of relaxation in smooth muscle surrounding the blood vessels. Smooth muscle is a type of non- Striated muscle, found within the Tunica media layer of large and small Arteries and Veins, the bladder 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). Myosins are a large family of Motor proteins found in Eukaryotic tissues. Thus, vasodilation 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. A symporter is an Integral membrane protein that is involved in movement of two or more different molecules or ions across a phospholipid membrane such as the Plasma membrane An antiporter (also called exchanger or counter-transporter) is an Integral membrane protein which is involved in Secondary active transport This is accomplished through retuptake of ions into the sarcoplasmic reticulum via exchangers and expulsion across the plasma membrane. The endoplasmic reticulum (Greek endo = "within" (prefix plásma = "formed entity" Latin reticulum = "little net" or ER, is an Organelle [2] The specific mechanisms to accomplish these effects varies from vasodilator to vasodilator.
These may be grouped as endogenous and exogenous. The word endogenous means "arising from within" the opposite of Exogenous. Exogenous (or exogeneous) (from the Greek words "exo" and "gen" meaning "outside" and "production" refers to an action or
Endogenous
| Vasodilators [3] | Receptor (↑ = opens. ↓ = closes) [3] | Transduction (↑ = increases. ↓ = decreases) [3] |
|---|---|---|
| EDHF | ? | hyperpolarization --> ↓VDCC --> ↓intracellular Ca2+ |
| depolarization | ↑Voltage-gated K+ channel | |
| interstitial K+ | directly | |
| nitric oxide | ↑NO receptor | ↑cGMP --> ↑PKG activity --> |
| β2 adrenergic agonists | β-2 adrenergic receptor | ↑Gs activity --> ↑AC activity --> ↑cAMP --> ↑PKA activity --> phosphorylation of MLCK --> ↓MLCK activity --> dephosphorylation of MLC |
| histamine | Histamine H2 receptor | |
| prostacyclin | IP receptor | |
| Prostaglandin D2 | DP receptor | |
| Prostaglandin E2 | EP receptor | |
| VIP | VIP receptor | ↑Gs activity --> ↑AC activity --> ↑cAMP --> ↑PKA activity -->
|
| (extracellular) adenosine | A1, A2a and A2b adenosine receptors | ↑ATP-sensitive K+ channel --> hyperpolarization --> close VDCC --> ↓intracellular Ca2+ |
| ↑P2Y receptor | activate Gq --> ↑PLC activity --> ↑intracellular Ca2+ --> ↑NOS activity --> ↑NO --> (see nitric oxide) | |
| L-Arginine | imidazoline and α-2 receptor? | Gi --> ↓cAMP --> activation of Na+/K+-ATPase[4] --> ↓intracellular Na2+ --> ↑Na+/Ca2+ exchanger activity --> ↓intracellular Ca2+ |
| Bradykinin | Bradykinin receptor | |
| Substance P Interestedperson (talk) 16:58, 27 March 2008 (UTC) | ||
| Niacin (nicotinic acid) | ||
| Platelet activating factor (PAF) | ||
| CO2 | - | ↓interstitial pH --> ?[5] |
| (probably) interstitial lactic acid | - | |
| muscle work | - |
|
Exogenous vasodilators
- Absence of high levels of environmental noise
- Absence of high levels of illumination
- Adenocard - Adenosine agonist, primarily used as an anti-arrhythmic. Endothelium-derived hyperpolarizing factor or EDHF refers to an unknown compound secreted by endothelial cells, which leads to Nitric oxide - and Prostacyclin Voltage-dependent calcium channels (VDCC are a group of voltage-gated Ion channels found in excitable cells ( e In biology depolarization is a decrease in the Absolute value of a cell's Membrane potential. Sodium channels are Integral membrane proteins that form Ion channels, conducting sodium ions ( Na+) through a cell's Plasma membrane Interstitial fluid (or tissue fluid) is a solution which bathes and surrounds the cells of multicellular animals Potassium (pəˈtæsiəm is a Chemical element. It has the symbol K (kalium from qalīy Atomic number 19 and Atomic mass 39 Nitric oxide or nitrogen monoxide is a Chemical compound with Chemical formula N[[Oxygen O]] Guanylate cyclase ( also known as guanylyl cyclase or GC) is a Lyase Enzyme. Cyclic guanosine monophosphate ( cGMP) is a Cyclic nucleotide derived from Guanosine triphosphate (GTP cGMP-dependent protein kinase or Protein Kinase G (PKG is a Serine/threonine-specific protein kinase that is activated by cGMP. Myosin-light-chain kinase (MLCK is a serine/threonine-specific protein kinase that Phosphorylates the regulatory light chain of Myosin II. SERCA stands for Sarco / Endoplasmic Reticulum Ca 2+- ATPase. The beta-2 adrenergic receptor (β2 adrenoreceptor also known as ADRB2, is an Beta-adrenergic receptor, and also denotes the human Gene encoding The beta-2 adrenergic receptor (β2 adrenoreceptor also known as ADRB2, is an Beta-adrenergic receptor, and also denotes the human Gene encoding The Gs alpha subunit (or Gs protein) is a Heterotrimeric G protein subunit which activates Adenylate cyclase. Adenylate cyclase ( also known as adenylyl cyclase or AC) is a Lyase Enzyme. Cyclic adenosine monophosphate ( cAMP, cyclic AMP or 3'-5'-cyclic Adenosine monophosphate) is a Second messenger that is important in many biological In Cell biology, protein kinase A, refers to a family of Enzymes whose activity is dependent on the level of Cyclic AMP (cAMP in the cell Myosin-light-chain kinase (MLCK is a serine/threonine-specific protein kinase that Phosphorylates the regulatory light chain of Myosin II. Histamine is a Biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a Neurotransmitter H2 receptors positively coupled to Adenylate cyclase via Gs. It is a potent stimulant of cAMP production Prostacyclin (or PGI2) is a member of the family of Lipid Molecules known as Eicosanoids. Prostacyclin receptor (or prostaglandin I2 receptor) is a receptor for Prostacyclin. Prostaglandin D2 is a Prostaglandin which binds to the receptor PTGDR. In Medicine, dinoprostone, is a naturally occurring Prostaglandin E2 (PGE2 Prostaglandin E2 receptor (53kDa also known as PTGER2, subtype EP2 or Prostaglandin E receptor 2, is a Prostaglandin receptor for Prostaglandin Vasoactive intestinal peptide ( VIP, also polypeptide) is a Peptide hormone containing 28 Amino acid residues and is produced in many There are two known receptors for the Vasoactive intestinal peptide (VIP termed VPAC1 and VPAC2 The Gs alpha subunit (or Gs protein) is a Heterotrimeric G protein subunit which activates Adenylate cyclase. Adenylate cyclase ( also known as adenylyl cyclase or AC) is a Lyase Enzyme. Cyclic adenosine monophosphate ( cAMP, cyclic AMP or 3'-5'-cyclic Adenosine monophosphate) is a Second messenger that is important in many biological In Cell biology, protein kinase A, refers to a family of Enzymes whose activity is dependent on the level of Cyclic AMP (cAMP in the cell Myosin-light-chain kinase (MLCK is a serine/threonine-specific protein kinase that Phosphorylates the regulatory light chain of Myosin II. Calcium-activated potassium channels are divided into BK channels IK channels and SK channels based on their conductance (big intermediate and small conductance Voltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's Membrane potential Voltage-dependent calcium channels (VDCC are a group of voltage-gated Ion channels found in excitable cells ( e Adenosine is a Nucleoside composed of a Molecule of Adenine attached to a Ribose sugar molecule ( Ribofuranose) moiety via a β-N9- The adenosine A1 receptor is one member of the Adenosine receptor group of G protein-coupled receptors with Adenosine as Endogenous The adenosine A2A receptor, also known as ADORA2A, is an Adenosine receptor, but also denotes the human Gene encoding it The adenosine A2b receptor, also known as ADORA2B, is an Adenosine receptor, and also denotes the human Gene incoding it The adenosine receptors (or P1 receptors) are a class of Purinergic receptors, G-protein coupled receptors with Adenosine as Endogenous Voltage-dependent calcium channels (VDCC are a group of voltage-gated Ion channels found in excitable cells ( e Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Adenosine diphosphate, abbreviated ADP, is a Nucleotide. It is an Ester of Pyrophosphoric acid with the Nucleoside Adenosine P2Y receptors are a family of Purinergic receptors G protein-coupled receptors stimulated by Nucleotides such as ATP, ADP, UTP Gq protein or Gq/11 is a Heterotrimeric G protein subunit that activates Phospholipase C (PLC A phospholipase is an enzyme that converts Phospholipids into Fatty acids and other Lipophilic substances Nitric oxide synthases ((NOSs are present among Eukaryotic enzymes as dimeric calmodulin-dependent or calmodulin-containing Cytochrome p450 -like Hemoprotein that Nitric oxide or nitrogen monoxide is a Chemical compound with Chemical formula N[[Oxygen O]] Arginine (abbreviated as Arg or R) is an α- Amino acid. The L-form is one of the 20 most common natural amino acids Imidazoline is a Nitrogen -containing heterocycle derived from Imidazole. The α2 receptor is a type of Adrenergic receptor. Effect The α2 receptor has several general functions in common with other α-receptors but also Gi alpha subunit (or Gi/G0 or Gi protein) is a Heterotrimeric G protein subunit which inhibits the production of Cyclic adenosine monophosphate ( cAMP, cyclic AMP or 3'-5'-cyclic Adenosine monophosphate) is a Second messenger that is important in many biological Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 The sodium-calcium exchanger (often denoted Na+/Ca2+ exchanger, NCX, or exchange protein) is an Antiporter Membrane Bradykinin is a Peptide that causes blood vessels to enlarge (dilate and therefore causes blood pressure to lower The bradykinin receptor is a receptor for Bradykinin. There are two Bradykinin receptors the B1 receptor and the B2 receptor. In Neuroscience, Substance P is a Neuropeptide: a short-chain Polypeptide that functions as a Neurotransmitter and as a Neuromodulator Niacin, also known as vitamin B3, is a water-soluble vitamin which prevents the deficiency disease Pellagra. Platelet-activating factor, also known as a PAF, PAF-acether or AGEPC (acetyl-glyceryl-ether-phosphorylcholine is a potent Phospholipid activator Carbon dioxide ( Chemical formula:) is a Chemical compound composed of two Oxygen Atoms covalently bonded to a single Interstitial fluid (or tissue fluid) is a solution which bathes and surrounds the cells of multicellular animals pH is the measure of the acidity or alkalinity of a Solution. Interstitial fluid (or tissue fluid) is a solution which bathes and surrounds the cells of multicellular animals Lactic acid ( IUPAC Systematic name: 2-hydroxypropanoic acid) also known as milk acid, is a Chemical compound that plays a role Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Adenosine is a Nucleoside composed of a Molecule of Adenine attached to a Ribose sugar molecule ( Ribofuranose) moiety via a β-N9- Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Carbon dioxide ( Chemical formula:) is a Chemical compound composed of two Oxygen Atoms covalently bonded to a single Interstitial fluid (or tissue fluid) is a solution which bathes and surrounds the cells of multicellular animals Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Adenosine diphosphate, abbreviated ADP, is a Nucleotide. It is an Ester of Pyrophosphoric acid with the Nucleoside Adenosine Interstitial fluid (or tissue fluid) is a solution which bathes and surrounds the cells of multicellular animals Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels particularly the large Arteries, Arterioles Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the Oxidative phosphorylation is a Metabolic pathway that uses energy released by the oxidation of Nutrients to produce Adenosine triphosphate (ATP Noise pollution (or environmental noise) is displeasing human- or machine-created sound that disrupts the activity or balance of human or animal life Over-illumination is the presence of lighting intensity ( Illuminance) beyond that required for a specified activity Dysrhythmia redirects here For the American band see Dysrhythmia (band.
- Alpha blockers (block the vasoconstricting effect of adrenaline). Alpha blockers (or adrenergic alpha-antagonists) are agents that act as antagonists of alpha adrenergic receptors Classification They can be divided Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels particularly the large Arteries, Arterioles
- Amyl nitrite and other nitrites are often used recreationally as a vasodilator, causing lightheadedness and a euphoric feeling. Amyl nitrite is the Chemical compound with the formula C5H11ONO
- Atrial natriuretic peptide (ANP) - a weak vasodilator. Atrial natriuretic peptide ( ANP) atrial natriuretic factor ( ANF) or atriopeptin, is a protein ( Polypeptide) Hormone secreted
- Ethanol
- Histamine-inducers
- Complement proteins C3a, C4a and C5a work by triggering histamine release from mast cells and basophil granulocytes. The complement system is a Biochemical cascade that helps clear Pathogens from an organism A mast cell (or mastocyte) is a resident cell of several types of tissues and contains many granules rich in Histamine and Heparin
- Nitric oxide inducers
- Glyceryl trinitrate (commonly known as Nitroglycerin)
- Isosorbide mononitrate & Isosorbide dinitrate
- Pentaerythritol Tetranitrate (PETN)
- Sodium nitroprusside
- PDE5 inhibitors: these agents indirectly increase the effects of nitric oxide
- Sildenafil (Viagra)
- Tadalafil
- Vardenafil
- Tetrahydrocannabinol (THC) - the major active chemical in marijuana. Nitroglycerin ( NG) ( US spelling also known as nitroglycerine, ( UK Spelling trinitroglycerin, trinitroglycerine Isosorbide mononitrate is a drug used principally in the treatment of Angina pectoris and acts by dilating the Blood vessels so as to reduce the Blood pressure Isosorbide dinitrate (ISDN (also known as Dilatrate is a Nitrate used pharmacologically as a vasodilator, e Pentaerythritol tetranitrate ( PETN, also known as pentrite, or rarely and primarily in German as nitropenta) is one of the most powerful high explosives Sodium nitroprusside is the Chemical compound with the formula Na2·2H2O A phosphodiesterase type 5 inhibitor, often shortened to PDE5 inhibitor, is a drug used to block the degradative action of Phosphodiesterase type 5 on Sildenafil citrate, sold as Viagra, Revatio and under various other trade names is a drug used to treat Erectile dysfunction (male impotence Tadalafil is an orally administered drug for treating impotence ( Erectile dysfunction) that initially was developed by the Biotechnology company ICOS Vardenafil ( INN) is a PDE5 inhibitor used for treating impotence ( Erectile dysfunction) that is sold under the trade name Levitra ( Bayer Medical cannabis refers to the use of the Cannabis plant as a physician-recommended Herbal therapy as well as synthetic THC and Cannabinoids Its mild vasodilating effects redden the eyes of cannabis smokers. Cannabis, also known as marijuana or marihuana, or ganja (from Hindi / Sanskrit: गांजा gānjā hemp) is a
- Theobromine. Theobromine, also known as xantheose, which also includes the similar compounds Theophylline and Caffeine.
- 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. Papaverine (pəˈpævəriːn is an Opium Alkaloid used primarily in the treatment of visceral Spasm, Vasospasm (especially those involving the The opium poppy, Papaver somniferum, is the type of Poppy from which Opium and many refined opiates such as Morphine, Thebaine Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Heart failure is a Cardiac condition that occurs when a problem with the structure or function of the Heart impairs its ability to supply [6] Flushing may be a physiological response to vasodilators. For a person to flush is to become markedly Red in the Face and often other areas of the skin from various physiological conditions
References
- ^ CVPharmacology
- ^ American Physiological Society
- ^ a b c Unless else specified in box, then ref is: Walter F. , PhD. Boron. Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3. Page 479
- ^ 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
- ^ Modin A, Björne H, Herulf M, Alving K, Weitzberg E, Lundberg JO (2001). "Nitrite-derived nitric oxide: a possible mediator of 'acidic-metabolic' vasodilation". Acta Physiol. Scand. 171 (1): 9–16. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11350258.
- ^ CVPharmacology
Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic