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 -->
  • phosphorylation of MLCK --> ↓MLCK activity --> dephosphorylation of MLC
  • SERCA --> ↓intracellular Ca2+
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+
  • (extracellular) ATP
  • (extracellular) ADP
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

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

  1. CVPharmacology
  2. American Physiological Society
  3. 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
  4. 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.
  5. 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
  6. 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.
  7. CVPharmacology
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