Editing Haemodynamic response (section)

==Mechanisms==
Various cell types play a role in HR, including astrocytes, smooth muscle cells, endothelial cells of blood vessels, and pericytes. These cells control whether the vessels are constricted or dilated, which dictates the amount of oxygen and glucose that is able to reach the neuronal tissue. 

[[File:Brain blood vasculature as a function of blood flow - journal.pbio.1001375.g001.png|thumb|left|Brain blood vasculature as a function of blood flow. Red arrows show vascular pruning, while white arrowheads indicate vessel widening in response to increased blood flow.<ref>{{cite journal | author = Sedwick C | year = 2012 | title = Pruning Brain Vasculature for Efficiency | journal = PLOS Biol | volume = 10 | issue = 8| page = e1001375 | doi = 10.1371/journal.pbio.1001375 | pmid = 22927793 | pmc = 3424260 | doi-access = free }}</ref>]]

===Astrocytes===
Astrocytes are unique in that they are intermediaries that lie between blood vessels and neurons. They are able to communicate with other astrocytes via [[gap junctions]] and have [[endfoot processes]] that interact with neuronal [[synapses]]. These processes have the ability to take up various [[neurotransmitters]], such as [[norepinephrine]] (NE) and [[glutamate]], and perform various other functions to maintain chemical and electrical [[homeostasis]] in the neuronal environment.

Constriction has been shown ''in vitro'' to occur when NE is placed in the synapse and is taken up by astrocyte receptors. NE uptake leads to an increase in intracellular astrocyte [[Ca2+|Ca{{sup|2+}}]]. When these calcium ion waves spread down the length of the astrocyte, [[Phospholipase A2|phospholipase A]] (PLA{{sub|2}}) is activated which in turn mobilizes [[arachidonic acid]]. These two compounds are transported to the smooth muscle and there react with [[cytochrome P450]] to make 20-hydroxyeicosatetraenoic acid (20-HETE), which acts through yet to-be-determined mechanisms to induce vasoconstriction. It has also been shown that [[agonists]] of [[metabotropic glutamate receptors]] (mGluR) also increase intracellular Ca{{sup|2+}} to produce constriction.<ref name="jap.physiology">{{cite journal | author = Koehler Raymond C | year = 2006 | title = Role of Astrocytes in Cerebrovascular Regulation | journal = Journal of Applied Physiology | volume = 100 | issue = 1| pages = 307–17 | doi=10.1152/japplphysiol.00938.2005| pmid = 16357084 | pmc = 1819408 }}</ref>

===Smooth muscle===

Dilation occurs when [[nitric oxide]] (NO) is released from endothelial cells and diffuses into nearby vascular smooth muscle. Several proposed pathways of NO-induced vasodilation have been proposed through haemodynamic investigation. It has been shown that NO inhibits 20-HETE synthesis, which may interfere with astrocytes' constriction pathways and lead to vasodilation. It has also been proposed that NO may amplify astrocyte Ca{{sup|2+}} influx and activate Ca{{sup|2+}}-dependent [[potassium channels]], releasing K{{sup|+}} into the interstitial space and inducing [[hyperpolarization (biology)|hyperpolarization]] of smooth muscle cells.<ref name="jap.physiology" /> In addition to this, it has already been shown that NO stimulates increased [[cyclic GMP]] (cGMP) levels in the smooth muscle cells, inducing a signaling cascade that results in the activation of [[cGMP-dependent protein kinase]] (PKG) and an ultimate decrease in smooth muscle Ca{{sup|2+}} concentration.<ref>{{cite journal |author1=Grange Robert W. |author2=Isotani Eiji | year = 2000 | title = Nitric Oxide Contributes to Vascular Smooth Muscle Relaxation in Contracting Fast-twitch Muscles | journal = Physiological Genomics | volume = 5 | issue = 1| pages = 35–44 |doi=10.1152/physiolgenomics.2001.5.1.35 |pmid=11161004 |s2cid=7117482 }}</ref> This leads to a decrease in muscle contraction and a subsequent dilation of the blood vessel. Whether the vessels are constricted or dilated dictates the amount of oxygen and glucose that is able to reach the neuronal tissue.

===Pericytes===

A principal function of pericytes is to interact with astrocytes, smooth muscle cells, and other intracranial cells to form the blood brain barrier and to modulate the size of blood vessels to ensure proper delivery and distribution of oxygen and nutrients to neuronal tissues. Pericytes have both [[cholinergic]] (α2) and [[adrenergic]] (β2) receptors. Stimulation of the latter leads to vessel relaxation, while stimulation of the cholinergic receptors leads to contraction.

Paracrine activity and oxygen availability have been shown to also modulate pericyte activity. The peptides [[angiotensin II]] and [[endothelin-1]] (ET-1) bind to pericytes and are vasoactive. Endothelial cells induce expression of endothelin-1, which leads to NO production and vasodilation. Experiments have demonstrated that oxygen levels also alter pericyte contraction and subsequent blood vessel contraction. In vitro, high oxygen concentrations cause pericyte constriction, while high [[CO2|CO{{sub|2}}]] concentrations cause relaxation. This suggests that pericytes may have the ability to dilate blood vessels when oxygen is in demand and constrict them when it is in surplus, modifying the rate of blood flow to tissues depending on their metabolic activity.<ref>{{cite journal |author1=Bergers Gabriele |author2=Song Steven | year = 2005 | title = The Role of Pericytes in Blood-vessel Formation and Maintenance | journal = Neuro-Oncology | volume = 7 | issue = 4| pages = 452–64 | pmc=1871727 | pmid=16212810 | doi=10.1215/S1152851705000232}}</ref>