Vasodilation

Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When vessels dilate, the flow of blood is increased due to a decrease in vascular resistance. Therefore, dilation of arterial blood vessels (mainly arterioles) leads to a decrease in blood pressure. The response may be intrinsic (due to local processes in the surrounding tissue) or extrinsic (due to hormones or the nervous system). Additionally, the response may either be localized to a specific organ (depending on the metabolic needs of a particular tissue, as during strenuous exercise), or systemic (seen throughout the entire systemic circulation). Factors that result in vasodilation are termed vasodilators.

Function

Vasodilation directly affects the relationship between mean arterial pressure, cardiac output and total peripheral resistance (TPR). Mathematically, cardiac output (blood flow measured in volume per unit time) is computed by multiplying the heart rate (in beats per minute) and the stroke volume (the volume of blood ejected during ventricular 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, with the TPR changing by the fourth power of the radius. An increase in either of these physiological components (cardiac output or TPR) cause a rise in the mean arterial pressure. Vasodilation works to decrease TPR and blood pressure through relaxation of smooth muscle cells in the tunica media layer of large arteries and smaller arterioles.

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 nitric oxide, bradykinin, potassium ions and 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 the result of relaxation in smooth muscle surrounding the blood vessels. This relaxation, in turn, relies on removing the stimulus for contraction, which depends on intracellular calcium ion concentrations and, consequently, phosphorylation of the light chain of the contractile protein myosin. Thus, vasodilation mainly works either by lowering intracellular calcium concentration or the dephosphorylation of myosin. 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 reuptake of ions into the sarcoplasmic reticulum via exchangers and expulsion across the plasma membrane. There are three main intracellular stimuli that can result in the vasodilation of blood vessels. The specific mechanism to accomplish these effects vary from vasodilator to vasodilator.

Class	Description	Example
Hyperpolarization mediated (Calcium channel blocker)	Changes in the resting membrane potential of the cell affects the level of intracellular calcium through modulation of voltage sensitive calcium channels in the plasma membrane.	adenosine
cAMP mediated	Adrenergic stimulation results in elevated levels of cAMP and protein kinase A, which results in increasing calcium removal from the cytoplasm	prostacyclin
cGMP mediated (Nitrovasodilator)	Through stimulation of protein kinase G	nitric oxide

PDE5 inhibitors and potassium channel openers can also have similar results.

Compounds that mediate the above mechanisms may be grouped as endogenous and exogenous.

Endogenous

Vasodilators	Receptor (↑ = opens. ↓ = closes) On vascular smooth muscle cells if not otherwise specified	Transduction (↑ = increases. ↓ = decreases)
EDHF	?	hyperpolarization --> ↓VDCC --> ↓intracellular Ca2+
depolarization	↑Voltage-gated K+ channel
interstitial K+	directly
nitric oxide	↑NO receptor on smooth muscle	↑cGMP --> ↑PKG activity --> phosphorylation of MLCK --> ↓MLCK activity --> dephosphorylation of MLC ↑SERCA --> ↓intracellular Ca2+
	NO receptor on endothelium	↓Endothelin synthesis
Noradrenaline	β-2 adrenergic receptor	↑Gs activity --> ↑AC activity --> ↑cAMP --> ↑PKA activity --> phosphorylation of MLCK --> ↓MLCK activity --> dephosphorylation of MLC
histamine	Histamine H1 receptor
prostacyclin	IP receptor
Prostaglandin D2	DP receptor
Prostaglandin E2	EP receptor
VIP	VIP receptor	↑Gs activity --> ↑AC activity --> ↑cAMP --> ↑PKA activity --> phosphorylation of MLCK --> ↓MLCK activity --> dephosphorylation of MLC open Ca2+-activated and voltage-gated K+channels --> hyperpolarization --> close VDCC --> ↓intracellular Ca2+
(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?	Gi --> ↓cAMP --> activation of Na+/K+-ATPase --> ↓intracellular Na+ --> ↑Na+/Ca2+ exchanger activity --> ↓intracellular Ca2+
Bradykinin	Bradykinin receptor
Substance P
Niacin (as nicotinic acid only)
Platelet activating factor (PAF)
CO2	-	↓interstitial pH --> ?
(probably) interstitial lactic acid	-
muscle work	-	↑vasodilators: ↑ATP consumption --> ↑adenosine ↑glucose usage --> CO2 ↑interstitial K+ ↑(extracellular) ATP ↑(extracellular) ADP ↑interstitial K+ ↓vasoconstrictors: ↑ATP consumption --> ↓ ATP (intracellular) ↓oxygen --> ↓oxidative phosphorylation --> ↓ ATP (intracellular)
Natriuretic peptides Prostaglandin I2 Prostaglandin E2 Heparin High shear stress	Various receptors on endothelium	↓Endothelin synthesis

• 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.
• Capsaicin
• 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
• Tetrahydrocannabinol (THC) - the major active chemical in marijuana. Its mild vasodilating effects redden the eyes of cannabis users.
• 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. Flushing may be a physiological response to vasodilators. Viagra, a phosphodiesterase inhibitor, works to increase blood flow in the penis through vasodilation. It may also be used to treat pulmonary arterial hypertension (PAH).

References

ca:Vasodilatació zh:血管舒張