Editing Blood pressure (section)

==Physiology==
[[File:Systolevs Diastole.png|thumb|Cardiac systole and diastole]]
[[File:VIM LDH.jpg|thumb|Blood flow velocity waveforms in the central retinal artery (red) and vein (blue), measured by [[laser Doppler imaging]] in the eye fundus of a healthy volunteer.|alt=]]
[[File:Circulation pressures v1.tif|thumb|Schematic of pressures in the circulation]]
During each heartbeat, blood pressure varies between a maximum (systolic) and a minimum (diastolic) pressure.<ref>{{cite web | title = Normal Blood Pressure Ranges in Adults | url = https://svollop.com/health/blood-pressure-ranges/ | website=svollop.com | date = 2023-03-16 | access-date = 2023-03-21 | archive-date = 2023-03-16 | archive-url = https://web.archive.org/web/20230316081326/https://svollop.com/health/blood-pressure-ranges/ | url-status = live }}</ref>{{Unreliable medical source|date=March 2023|sure=y}} The blood pressure in the circulation is principally due to the pumping action of the heart.<ref name = 'Caro'>{{cite book | vauthors = Caro CG |title=The Mechanics of The Circulation |publisher=Oxford University Press |location=Oxford [Oxfordshire] |year=1978 |isbn=978-0-19-263323-1}}</ref> However, blood pressure is also regulated by neural regulation from the brain (see [[Hypertension and the brain]]), as well as osmotic regulation from the kidney. Differences in mean blood pressure drive the flow of blood around the circulation. The rate of mean blood flow depends on both blood pressure and the resistance to flow presented by the blood vessels. In the absence of [[Fluid statics|hydrostatic]] effects (e.g. standing), mean blood pressure decreases as the [[Circulatory system|circulating blood]] moves away from the heart through arteries and [[capillaries]] due to [[Viscosity|viscous]] losses of energy. Mean blood pressure drops over the whole circulation, although most of the fall occurs along the small arteries and [[arterioles]].<ref name='Klabunde2005p93-4'>{{cite book | vauthors = Klabunde R | title = Cardiovascular Physiology Concepts | publisher = Lippincott Williams & Wilkins | year = 2005 | pages = 93–94 | isbn = 978-0-7817-5030-1 }}</ref> Pulsatility also diminishes in the smaller elements of the arterial circulation, although some transmitted pulsatility is observed in capillaries.<ref>{{cite journal | vauthors = Mahler F, Muheim MH, Intaglietta M, Bollinger A, Anliker M | title = Blood pressure fluctuations in human nailfold capillaries | journal = The American Journal of Physiology | volume = 236 | issue = 6 | pages = H888–H893 | date = June 1979 | pmid = 443454 | doi = 10.1152/ajpheart.1979.236.6.H888 }}</ref> Gravity affects blood pressure via hydrostatic forces (e.g., during standing), and valves in veins, [[breathing]], and pumping from contraction of skeletal muscles also influence blood pressure, particularly in veins.<ref name = 'Caro'/>

===Hemodynamics===
{{main|Hemodynamics}}
A simple view of the [[hemodynamics]] of systemic arterial pressure is based around [[mean arterial pressure]] (MAP) and pulse pressure. Most influences on blood pressure can be understood in terms of their effect on [[cardiac output]],<ref>{{cite journal | vauthors = Guyton AC | title = The relationship of cardiac output and arterial pressure control | journal = Circulation | volume = 64 | issue = 6 | pages = 1079–1088 | date = December 1981 | pmid = 6794930 | doi = 10.1161/01.cir.64.6.1079 | doi-access = free }}</ref> [[Vascular resistance|systemic vascular resistance]], or [[arterial stiffness]] (the inverse of arterial compliance). Cardiac output is the product of stroke volume and heart rate. Stroke volume is influenced by 1) the [[end-diastolic volume]] or filling pressure of the ventricle acting via the [[Frank–Starling law|Frank–Starling mechanism]]—this is influenced by [[blood volume]]; 2) [[Myocardial contractility|cardiac contractility]]; and 3) [[afterload]], the impedance to blood flow presented by the circulation.<ref>{{cite journal | vauthors = Milnor WR | title = Arterial impedance as ventricular afterload | journal = Circulation Research | volume = 36 | issue = 5 | pages = 565–570 | date = May 1975 | pmid = 1122568 | doi = 10.1161/01.res.36.5.565 | doi-access = free }}</ref> In the short-term, the greater the blood volume, the higher the cardiac output. This has been proposed as an explanation of the relationship between high dietary salt intake and increased blood pressure; however, responses to increased dietary sodium intake vary between individuals and are highly dependent on autonomic nervous system responses and the [[renin–angiotensin system]],<ref>{{cite journal | vauthors = Freis ED | title = Salt, volume and the prevention of hypertension | journal = Circulation | volume = 53 | issue = 4 | pages = 589–595 | date = April 1976 | pmid = 767020 | doi = 10.1161/01.CIR.53.4.589 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Caplea A, Seachrist D, Dunphy G, Ely D | title = Sodium-induced rise in blood pressure is suppressed by androgen receptor blockade | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 280 | issue = 4 | pages = H1793–H1801 | date = April 2001 | pmid = 11247793 | doi = 10.1152/ajpheart.2001.280.4.H1793 | series = 4 | s2cid = 12069178 }}</ref><ref>{{cite journal | vauthors = Houston MC | title = Sodium and hypertension. A review | journal = Archives of Internal Medicine | volume = 146 | issue = 1 | pages = 179–185 | date = January 1986 | pmid = 3510595 | doi = 10.1001/archinte.1986.00360130217028 | series = 1 }}</ref> changes in [[Plasma osmolality|plasma osmolarity]] may also be important.<ref>{{cite journal | vauthors = Kanbay M, Aslan G, Afsar B, Dagel T, Siriopol D, Kuwabara M, Incir S, Camkiran V, Rodriguez-Iturbe B, Lanaspa MA, Covic A, Johnson RJ | display-authors = 6 | title = Acute effects of salt on blood pressure are mediated by serum osmolality | journal = Journal of Clinical Hypertension | volume = 20 | issue = 10 | pages = 1447–1454 | date = October 2018 | pmid = 30232829 | pmc = 8030773 | doi = 10.1111/jch.13374 | doi-access = free }}</ref> In the longer-term the relationship between volume and blood pressure is more complex.<ref>{{cite journal | vauthors = Titze J, Luft FC | title = Speculations on salt and the genesis of arterial hypertension | journal = Kidney International | volume = 91 | issue = 6 | pages = 1324–1335 | date = June 2017 | pmid = 28501304 | doi = 10.1016/j.kint.2017.02.034 | doi-access = free }}</ref> In simple terms, systemic vascular resistance is mainly determined by the caliber of small arteries and arterioles. The resistance attributable to a blood vessel depends on its radius as described by the [[Hagen–Poiseuille equation|Hagen-Poiseuille's equation]]  (resistance∝1/radius<sup>4</sup>). Hence, the smaller the radius, the higher the resistance. Other physical factors that affect resistance include: vessel length (the longer the vessel, the higher the resistance), blood viscosity (the higher the viscosity, the higher the resistance)<ref>{{cite journal | vauthors = Lee AJ | title = The role of rheological and haemostatic factors in hypertension | journal = Journal of Human Hypertension | volume = 11 | issue = 12 | pages = 767–776 | date = December 1997 | pmid = 9468002 | doi = 10.1038/sj.jhh.1000556 | doi-access = free }}</ref> and the number of vessels, particularly the smaller numerous, arterioles and capillaries. The presence of a severe arterial [[stenosis]] increases resistance to flow, however this increase in resistance rarely increases systemic blood pressure because its contribution to total systemic resistance is small, although it may profoundly decrease downstream flow.<ref>{{cite journal | vauthors = Coffman JD | title = Pathophysiology of obstructive arterial disease | journal = Herz | volume = 13 | issue = 6 | pages = 343–350 | date = December 1988 | pmid = 3061915 }}</ref> Substances called [[vasoconstrictor]]s reduce the caliber of blood vessels, thereby increasing blood pressure. [[Vasodilator]]s (such as [[nitroglycerin]]) increase the caliber of blood vessels, thereby decreasing arterial pressure. In the longer term a process termed remodeling also contributes to changing the caliber of small blood vessels and influencing resistance and reactivity to vasoactive agents.<ref>{{cite journal | vauthors = Korner PI, Angus JA | title = Structural determinants of vascular resistance properties in hypertension. Haemodynamic and model analysis | journal = Journal of Vascular Research | volume = 29 | issue = 4 | pages = 293–312 | date = 1992 | pmid = 1391553 | doi = 10.1159/000158945 }}</ref><ref>{{cite journal | vauthors = Mulvany MJ | title = Small artery remodelling in hypertension | journal = Basic & Clinical Pharmacology & Toxicology | volume = 110 | issue = 1 | pages = 49–55 | date = January 2012 | pmid = 21733124 | doi = 10.1111/j.1742-7843.2011.00758.x | doi-access = free }}</ref> Reductions in capillary density, termed capillary rarefaction, may also contribute to increased resistance in some circumstances.<ref>{{cite journal | vauthors = de Moraes R, Tibirica E | title = Early Functional and Structural Microvascular Changes in Hypertension Related to Aging | journal = Current Hypertension Reviews | volume = 13 | issue = 1 | pages = 24–32 | date = 2017 | pmid = 28412915 | doi = 10.2174/1573402113666170413095508 }}</ref>

In practice, each individual's autonomic nervous system and other systems regulating blood pressure, notably the kidney,<ref>{{cite journal | vauthors = Guyton AC, Coleman TG, Cowley AV, Scheel KW, Manning RD, Norman RA | title = Arterial pressure regulation. Overriding dominance of the kidneys in long-term regulation and in hypertension | journal = The American Journal of Medicine | volume = 52 | issue = 5 | pages = 584–594 | date = May 1972 | pmid = 4337474 | doi = 10.1016/0002-9343(72)90050-2 }}</ref> respond to and regulate all these factors so that, although the above issues are important, they rarely act in isolation and the actual arterial pressure response of a given individual can vary widely in the short and long term.

===Pulse pressure===
{{main|Pulse pressure}}
[[File:Arterial-blood-pressure-curve.svg|thumb|A schematic representation of the arterial pressure waveform over one cardiac cycle. The notch in the curve is associated with closing of the aortic valve.]]
The pulse pressure is the difference between the measured systolic and diastolic pressures,<ref name = KlabundePulse2007 />

:::::::::::<math>\! P_{\text{pulse}} = P_{\text{sys}} - P_{\text{dias}}.</math>

The pulse pressure is a consequence of the pulsatile nature of the [[cardiac output]], i.e. the heartbeat. The magnitude of the pulse pressure is usually attributed to the interaction of the [[stroke volume]] of the heart, the compliance (ability to expand) of the arterial system—largely attributable to the [[aorta]] and large elastic arteries—and the [[Drag (physics)|resistance]] to flow in the [[arterial tree]].<ref name=KlabundePulse2007>{{cite web |url=http://www.cvphysiology.com/Blood%20Pressure/BP003.htm |title=Cardiovascular Physiology Concepts – Pulse Pressure |access-date=2008-10-02 | vauthors = Klabunde RE |year=2007 |url-status=dead |archive-url=https://web.archive.org/web/20091018055524/http://www.cvphysiology.com/Blood%20Pressure/BP003.htm |archive-date=2009-10-18 }}</ref>

====Clinical significance of pulse pressure====
A healthy pulse pressure is around 40 mmHg.<ref name="Homan Cichowski 2019"/> A pulse pressure that is consistently 60 mmHg or greater is likely to be associated with disease, and a pulse pressure of 50 mmHg or more increases the risk of [[cardiovascular disease]] as well as other complications such as eye and kidney disease.<ref name="Cleveland Clinic 2021">{{cite web |url=https://my.clevelandclinic.org/health/symptoms/21629-pulse-pressure |title= Pulse pressure  |author=<!--Not stated--> |date=28 July 2021 |publisher=Cleveland Clinic |access-date=10 February 2023 }}</ref> Pulse pressure is considered low if it is less than 25% of the systolic. (For example, if the systolic pressure is 120 mmHg, then the pulse pressure would be considered low if it is less than 30 mmHg, since 30 is 25% of 120.)<ref name="pmid21848774">{{cite journal | vauthors = Liaw SY, Scherpbier A, Klainin-Yobas P, Rethans JJ | title = A review of educational strategies to improve nurses' roles in recognizing and responding to deteriorating patients | journal = International Nursing Review | volume = 58 | issue = 3 | pages = 296–303 | date = September 2011 | pmid = 21848774 | doi = 10.1111/j.1466-7657.2011.00915.x }}</ref> A very low pulse pressure can be a symptom of disorders such as [[congestive heart failure]].<ref name="Cleveland Clinic 2021"/>

Elevated pulse pressure has been found to be a stronger independent predictor of cardiovascular events, especially in older populations, than has systolic, diastolic, or mean arterial pressure.<ref name="Cleveland Clinic 2021"/><ref name="Mitchell Izzo Lacourcière Ouellet 2002 pp. 2955–2961">{{cite journal | last1=Mitchell | first1=Gary F. | last2=Izzo | first2=Joseph L. | last3=Lacourcière | first3=Yves | last4=Ouellet | first4=Jean-Pascal | last5=Neutel | first5=Joel | last6=Qian | first6=Chunlin | last7=Kerwin | first7=Linda J. | last8=Block | first8=Alan J. | last9=Pfeffer | first9=Marc A. | title=Omapatrilat Reduces Pulse Pressure and Proximal Aortic Stiffness in Patients With Systolic Hypertension | journal=Circulation | publisher=Ovid Technologies (Wolters Kluwer Health) | volume=105 | issue=25 | date=25 Jun 2002 | issn=0009-7322 | doi=10.1161/01.cir.0000020500.77568.3c | pages=2955–2961| pmid=12081987 | s2cid=7092379 }}</ref> This increased risk exists for both men and women and even when no other cardiovascular risk factors are present. The increased risk also exists even in cases in which diastolic pressure decreases over time while systolic remains steady.<ref name="Franklin Khan Wong Larson 1999 pp. 354–360">{{cite journal | last1=Franklin | first1=Stanley S. | last2=Khan | first2=Shehzad A. | last3=Wong | first3=Nathan D. | last4=Larson | first4=Martin G. | last5=Levy | first5=Daniel | title=Is Pulse Pressure Useful in Predicting Risk for Coronary Heart Disease? | journal=Circulation | publisher=Ovid Technologies (Wolters Kluwer Health) | volume=100 | issue=4 | date=27 Jul 1999 | issn=0009-7322 | doi=10.1161/01.cir.100.4.354 | pages=354–360| pmid=10421594 | doi-access=free }}</ref><ref name="Benetos Safar Rudnichi Smulyan 1997 pp. 1410–1415">{{cite journal | last1=Benetos | first1=Athanase | last2=Safar | first2=Michel | last3=Rudnichi | first3=Annie | last4=Smulyan | first4=Harold | last5=Richard | first5=Jacques-Lucien | last6=Ducimetière | first6=Pierre | last7=Guize | first7=Louis | title=Pulse Pressure | journal=Hypertension | publisher=Ovid Technologies (Wolters Kluwer Health) | volume=30 | issue=6 | year=1997 | issn=0194-911X | doi=10.1161/01.hyp.30.6.1410 | pages=1410–1415| pmid=9403561 }}</ref>

A [[meta-analysis]] in 2000 showed that a 10&nbsp;mmHg increase in pulse pressure was associated with a 20% increased risk of cardiovascular mortality, and a 13% increase in risk for all coronary end points. The study authors also noted that, while risks of cardiovascular end points do increase with higher systolic pressures, at any given systolic blood pressure the risk of major cardiovascular end points increases, rather than decreases, with lower diastolic levels. This suggests that interventions that lower diastolic pressure without also lowering systolic pressure (and thus lowering pulse pressure) could actually be counterproductive.<ref name = "pulse pressure not mean">{{cite journal | vauthors = Blacher J, Staessen JA, Girerd X, Gasowski J, Thijs L, Liu L, Wang JG, Fagard RH, Safar ME | display-authors = 6 | title = Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients | journal = Archives of Internal Medicine | volume = 160 | issue = 8 | pages = 1085–1089 | date = April 2000 | pmid = 10789600 | doi = 10.1001/archinte.160.8.1085 | doi-access = free }}</ref> There are no drugs currently approved to lower pulse pressure, although some antihypertensive drugs may modestly lower pulse pressure, while in some cases a drug that lowers overall blood pressure may actually have the counterproductive side effect of raising pulse pressure.<ref name="cushman">{{cite journal |last1=Cushman |first1=William C. |last2=Materson |first2=Barry J. |last3=Williams |first3=David W. |last4=Reda |first4=Domenic J. |date=1 Oct 2001 |title=Pulse Pressure Changes With Six Classes of Antihypertensive Agents in a Randomized, Controlled Trial |journal=Hypertension |volume=38 |issue=4 |pages=953–957 |doi=10.1161/hy1001.096212|pmid=11641316|doi-access=free }}</ref>

Pulse pressure can both widen or narrow in people with [[sepsis]] depending on the degree of [[hemodynamic]] compromise. A pulse pressure of over 70 mmHg in sepsis is correlated with an increased chance of survival and a more positive response to [[Fluid replacement#Intravenous|IV fluids]].<ref name=pedsepsis>{{cite journal |vauthors=Khilnani P, Singhi S, Lodha R, Santhanam I, Sachdev A, Chugh K, Jaishree M, Ranjit S, Ramachandran B, Ali U, Udani S, Uttam R, Deopujari S |date=January 2010 |title=Pediatric Sepsis Guidelines: Summary for resource-limited countries |journal=Indian J Crit Care Med |volume=14 |issue=1 |pages=41–52 |doi=10.4103/0972-5229.63029 |pmc=2888329 |pmid=20606908 |doi-access=free }}</ref><ref name=widesepsis>{{cite journal |vauthors=Al-Khalisy H, Nikiforov I, Jhajj M, Kodali N, Cheriyath P |date=11 December 2015 |title=A widened pulse pressure: a potential valuable prognostic indicator of mortality in patients with sepsis. J Community Hosp Intern Med Perspect |journal=J Community Hosp Intern Med Perspect |volume=5 |issue=6 |page=29426 |doi=10.3402/jchimp.v5.29426 |pmc=4677588 |pmid=26653692 }}</ref>

===Mean arterial pressure===
{{main|Mean arterial pressure}}
[[Mean arterial pressure]] (MAP) is the average of blood pressure over a [[cardiac cycle]] and is determined by the [[cardiac output]] (CO), [[systemic vascular resistance]] (SVR), and [[central venous pressure]] (CVP):<ref name="Mayet Hughes 2003 pp. 1104–9"/><ref name="Granger Hall 2007 pp. 241–263">{{cite book |  vauthors = Granger JP, Hall JE | title=Comprehensive Hypertension | chapter=Role of the Kidney in Hypertension | publisher=Elsevier | year=2007 | isbn=978-0-323-03961-1 | doi=10.1016/b978-0-323-03961-1.50026-x | pages=241–263}}</ref><ref name=KlabundeMAP2007>{{cite web |url=http://www.cvphysiology.com/Blood%20Pressure/BP006.htm |title=Cardiovascular Physiology Concepts – Mean Arterial Pressure |access-date=2008-09-29 | vauthors = Klabunde RE |year=2007 |url-status=dead |archive-url=https://web.archive.org/web/20091002040008/http://www.cvphysiology.com/Blood%20Pressure/BP006.htm |archive-date=2009-10-02 }}</ref>

:::::::::::<math>\! \text{MAP} = (\text{CO} \cdot \text{SVR}) + \text{CVP} </math>

In practice, the contribution of CVP (which is small) is generally ignored and so

:::::::::::<math>\! \text{MAP} = \text{CO} \cdot \text{SVR} </math>

MAP is often estimated from measurements of the systolic pressure,  <math> \! P_{\text{sys}}</math> and the diastolic pressure,  <math> \! P_{\text{dias}}</math>&nbsp;<ref name="KlabundeMAP2007" /> using the equation:

<math>\! \text{MAP} \approxeq P_{\text{dias}} + k (P_{\text{sys}} - P_{\text{dias}})</math>

where ''k'' = 0.333 although other values for ''k'' have been advocated.<ref>{{cite journal | vauthors = Bos WJ, Verrij E, Vincent HH, Westerhof BE, Parati G, van Montfrans GA | title = How to assess mean blood pressure properly at the brachial artery level | journal = Journal of Hypertension | volume = 25 | issue = 4 | pages = 751–755 | date = April 2007 | pmid = 17351365 | doi = 10.1097/HJH.0b013e32803fb621 | s2cid = 23155959 }}</ref><ref>{{cite journal | vauthors = Meaney E, Alva F, Moguel R, Meaney A, Alva J, Webel R | title = Formula and nomogram for the sphygmomanometric calculation of the mean arterial pressure | journal = Heart | volume = 84 | issue = 1 | pages = 64 | date = July 2000 | pmid = 10862592 | pmc = 1729401 | doi = 10.1136/heart.84.1.64 }}</ref>

===Regulation of blood pressure===
{{See also|Renin–angiotensin system}}
The [[endogenous]], [[Homeostasis|homeostatic]] regulation of arterial pressure is not completely understood, but the following mechanisms of regulating arterial pressure have been well-characterized:
* [[Baroreceptor reflex]]: [[Baroreceptor]]s in the [[high pressure receptor zones]] detect changes in arterial pressure. These baroreceptors send signals ultimately to the [[medulla oblongata|medulla of the brain stem]], specifically to the [[rostral ventrolateral medulla]] (RVLM). The medulla, by way of the [[autonomic nervous system]], adjusts the mean arterial pressure by altering both the force and speed of the heart's contractions, as well as the systemic vascular resistance. The most important arterial baroreceptors are located in the left and right [[carotid sinus]]es and in the [[aortic arch]].<ref name='KlabundeArtBar2007'>{{cite web |url=http://www.cvphysiology.com/Blood%20Pressure/BP012.htm |title=Cardiovascular Physiology Concepts – Arterial Baroreceptors |access-date=2008-09-09 |vauthors=Klabunde RE |year=2007 |archive-date=2009-12-23 |archive-url=https://web.archive.org/web/20091223020230/http://www.cvphysiology.com/Blood%20Pressure/BP012.htm |url-status=live }}</ref>
* [[Renin–angiotensin system]] (RAS): This system is generally known for its long-term adjustment of arterial pressure. This system allows the [[kidney]] to compensate for loss in [[blood volume]] or drops in arterial pressure by activating an endogenous [[vasoconstrictor]] known as [[angiotensin II]].
* [[Aldosterone]] release: This [[steroid hormone]] is released from the [[adrenal cortex]] in response to activation of the renin-angiotensin system, high serum [[potassium]] levels, or elevated [[Adrenocorticotropic hormone|adrenocorticotropic hormone (ACTH)]]. Renin converts angiotensinogen to angiotensin I, which is converted by [[Angiotensin-converting enzyme|angiotensin converting enzyme]] to angiotensin II. Angiotensin II then signals to the adrenal cortex to release aldosterone.<ref>{{cite book |vauthors=Fountain J, Lappin SL |chapter=Physiology, Renin Angiotensin System. |date=January 2022 |title=StatPearls |publisher=StatPearls Publishing |location=Treasure Island, FL |pmid=29261862 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK470410/ |access-date=18 November 2022 |archive-date=29 April 2019 |archive-url=https://web.archive.org/web/20190429200530/https://www.ncbi.nlm.nih.gov/books/NBK470410/ |url-status=live }}</ref> Aldosterone stimulates [[sodium]] retention and potassium excretion by the kidneys and the consequent salt and water retention increases plasma volume, and indirectly, arterial pressure. Aldosterone may also exert direct pressor effects on vascular smooth muscle and central effects on sympathetic nervous system activity.<ref>{{cite journal | vauthors = Feldman RD | title = Aldosterone and blood pressure regulation: recent milestones on the long and winding road from electrocortin to KCNJ5, GPER, and beyond | journal = Hypertension | volume = 63 | issue = 1 | pages = 19–21 | date = January 2014 | pmid = 24191283 | doi = 10.1161/HYPERTENSIONAHA.113.01251 | doi-access = free }}</ref>
* [[Baroreceptor]]s in [[low pressure receptor zones]] (mainly in the [[venae cavae]] and the [[pulmonary veins]], and in the [[atrium (heart)|atria]]) result in feedback by regulating the secretion of [[antidiuretic hormone]] (ADH/vasopressin), [[renin]] and [[aldosterone]]. The resultant increase in [[blood volume]] results in an increased [[cardiac output]] by the [[Frank–Starling law of the heart]], in turn increasing arterial blood pressure.

These different mechanisms are not necessarily independent of each other, as indicated by the link between the RAS and aldosterone release. When blood pressure falls many physiological cascades commence in order to return the blood pressure to a more appropriate level.

# The blood pressure fall is detected by a decrease in blood flow and thus a decrease in [[glomerular filtration rate]] (GFR).
# Decrease in GFR is sensed as a decrease in Na<sup>+</sup> levels by the [[macula densa]].
# The macula densa causes an increase in Na<sup>+</sup> reabsorption, which causes water to follow in via [[osmosis]] and leads to an ultimate increase in [[blood plasma|plasma]] volume. Further, the macula densa releases adenosine which causes constriction of the afferent arterioles.
# At the same time,  the [[juxtaglomerular cells]] sense the decrease in blood pressure and release [[renin]].
# Renin converts [[angiotensinogen]] (inactive form) to [[angiotensin I]] (active form).
# Angiotensin I flows in the bloodstream until it reaches the capillaries of the lungs where [[angiotensin-converting enzyme]] (ACE) acts on it to convert it into [[angiotensin II]].
# Angiotensin II is a vasoconstrictor that will increase blood flow to the heart and subsequently the preload, ultimately increasing the [[cardiac output]].
# Angiotensin II also causes an increase in the release of [[aldosterone]] from the [[adrenal gland]]s.
# Aldosterone further increases the Na<sup>+</sup> and H<sub>2</sub>O reabsorption in the [[distal convoluted tubule]] of the [[nephron]].

The RAS is targeted pharmacologically by [[ACE inhibitor]]s and [[angiotensin II receptor antagonist]]s (also known as angiotensin receptor blockers; ARB). The aldosterone system is directly targeted by [[aldosterone antagonist]]s. The fluid retention may be targeted by [[diuretic]]s; the antihypertensive effect of diuretics is due to its effect on blood volume. Generally, the baroreceptor reflex is not targeted in [[hypertension]] because if blocked, individuals may experience [[orthostatic hypotension]] and [[fainting]].