Vasodilator
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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) lead 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.[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. 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 glands, 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, 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. This is accomplished through retuptake of ions into the sarcoplasmic reticulum via exchangers and expulsion across the plasma membrane. [2] The specific mechanisms to accomplish these effects varies from vasodilator to vasodilator.
These may be grouped as endogenous and exogenous vasodilators;
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 | prostacyclin receptor | |
| Prostaglandin D2 | PGD2 receptor | |
| Prostaglandin E2 | PGE2 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? [4] | Gi --> ↓cAMP --> activation of Na+/K+-ATPase[5] --> ↓intracellular Na2+ --> ↑Na+/Ca2+ exchanger activity --> ↓intracellular Ca2+ |
| Bradykinin | Bradykinin receptor | |
| Niacin (nicotinic acid) | ||
| Platelet activating factor (PAF) | ||
| CO2 | - | ↓interstitial pH --> ?[6] |
| (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.
- Alpha blockers (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 proteins C3a, C4a and C5a work by triggering histamine release from mast cells and basophil granulocytes.
- 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
- Terbutaline
- Tetrahydrocannabinol (THC) - the major active chemical in marijuana. Its mild vasodilating effects redden the eyes of cannabis smokers.
- Theobromine.
- Papaverine an alkaloid found in the opium poppy papaver somniferum
- Conjugated estrogens
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 a maintaining a lower blood pressure reduces the patient's risk of developing other cardiac problems.[7] Flushing may be a physiological response to vasodilators.
References
- ↑ CVPharmacology
- ↑ American Physiological Society
- ↑ 3.0 3.1 3.2 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
- ↑ Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells Mahesh S. Joshi*,{dagger}, T. Bruce Ferguson, Jr.*, Fruzsina K. Johnson{ddagger}, Robert A. Johnson{ddagger}, Sampath Parthasarathy§, and Jack R. Lancaster, Jr.
- ↑ 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. PMID 11350258.
- ↑ CVPharmacology
Template:Peripheral vasodilators
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