Editing Hypertension (section)

==Pathophysiology==
{{Main|Pathophysiology of hypertension}}
[[File:Mean arterial pressure.png|thumb|upright=1.4|Determinants of mean arterial pressure]]
[[File:Blausen 0486 HighBloodPressure 01.png|thumb|upright=1.4|Illustration depicting the effects of high blood pressure]]
In most people with established [[essential (primary) hypertension|essential hypertension]], increased resistance to blood flow ([[total peripheral resistance]]) accounts for the high pressure while [[cardiac output]] remains normal.<ref>{{cite journal | vauthors = Conway J | title = Hemodynamic aspects of essential hypertension in humans | journal = Physiological Reviews | volume = 64 | issue = 2 | pages = 617–660 | date = April 1984 | pmid = 6369352 | doi = 10.1152/physrev.1984.64.2.617 }}</ref> There is evidence that some younger people with [[prehypertension]] or 'borderline hypertension' have high cardiac output, an elevated heart rate and normal peripheral resistance, termed hyperkinetic borderline hypertension.<ref name = Palatini>{{cite journal | vauthors = Palatini P, Julius S | title = The role of cardiac autonomic function in hypertension and cardiovascular disease | journal = Current Hypertension Reports | volume = 11 | issue = 3 | pages = 199–205 | date = June 2009 | pmid = 19442329 | doi = 10.1007/s11906-009-0035-4 | s2cid = 11320300 }}</ref> These individuals may develop the typical features of established essential hypertension in later life as their cardiac output falls and peripheral resistance rises with age.<ref name = Palatini /> Whether this pattern is typical of all people who ultimately develop hypertension is disputed.<ref>{{cite journal | vauthors = Andersson OK, Lingman M, Himmelmann A, Sivertsson R, Widgren BR | title = Prediction of future hypertension by casual blood pressure or invasive hemodynamics? A 30-year follow-up study | journal = Blood Pressure | volume = 13 | issue = 6 | pages = 350–354 | year = 2004 | pmid = 15771219 | doi = 10.1080/08037050410004819 | s2cid = 28992820 }}</ref> The increased peripheral resistance in established hypertension is mainly attributable to structural narrowing of small arteries and [[arteriole]]s,<ref>{{cite journal | vauthors = Folkow B | title = Physiological aspects of primary hypertension | journal = Physiological Reviews | volume = 62 | issue = 2 | pages = 347–504 | date = April 1982 | pmid = 6461865 | doi = 10.1152/physrev.1982.62.2.347 }}</ref> although a reduction in the number or density of capillaries may also contribute.<ref>{{cite journal | vauthors = Struijker Boudier HA, le Noble JL, Messing MW, Huijberts MS, le Noble FA, van Essen H | title = The microcirculation and hypertension | journal = Journal of Hypertension Supplement | volume = 10 | issue = 7 | pages = S147–156 | date = December 1992 | pmid = 1291649 | doi = 10.1097/00004872-199212000-00016 }}</ref>

It is unclear whether or not [[vasoconstriction]] of arteriolar blood vessels plays a role in hypertension.<ref>{{cite journal | vauthors = Schiffrin EL | title = Reactivity of small blood vessels in hypertension: relation with structural changes. State of the art lecture | journal = Hypertension | volume = 19 | issue = 2 Suppl | pages = II1-9 | date = February 1992 | pmid = 1735561 | doi = 10.1161/01.HYP.19.2_Suppl.II1-a | doi-access = free }}</ref> Hypertension is also associated with decreased peripheral [[Compliance (physiology)|venous compliance]],<ref>{{cite journal | vauthors = Safar ME, London GM | title = Arterial and venous compliance in sustained essential hypertension | journal = Hypertension | volume = 10 | issue = 2 | pages = 133–139 | date = August 1987 | pmid = 3301662 | doi = 10.1161/01.HYP.10.2.133 | doi-access = free }}</ref> which may increase [[venous return]], increase cardiac [[Preload (cardiology)|preload]] and, ultimately, cause [[diastolic dysfunction]]. For patients having hypertension, higher [[heart rate variability]] (HRV) is a risk factor for [[atrial fibrillation]].<ref name="pmid35260686">{{cite journal | vauthors = Kim SH, Lim KR, Chun KJ | title=Higher heart rate variability as a predictor of atrial fibrillation in patients with hypertensione | journal= [[Scientific Reports]] | volume=12 | issue=1 | pages=3702 | year=2022 | doi= 10.1038/s41598-022-07783-3 | pmc=8904557 | pmid=35260686 | bibcode=2022NatSR..12.3702K }}</ref>

[[Pulse pressure]] (the difference between systolic and diastolic blood pressure) is frequently increased in older people with hypertension.<ref>{{cite journal | vauthors = Steppan J, Barodka V, Berkowitz DE, Nyhan D | title = Vascular stiffness and increased pulse pressure in the aging cardiovascular system | journal = Cardiology Research and Practice | volume = 2011 | pages = 263585 | date = 2011-08-02 | pmid = 21845218 | pmc = 3154449 | doi = 10.4061/2011/263585 | doi-access = free }}</ref> This can mean that systolic pressure is abnormally high, but diastolic pressure may be normal or low, a condition termed [[isolated systolic hypertension]].<ref>{{cite journal | vauthors = Chobanian AV | title = Clinical practice. Isolated systolic hypertension in the elderly | journal = The New England Journal of Medicine | volume = 357 | issue = 8 | pages = 789–796 | date = August 2007 | pmid = 17715411 | doi = 10.1056/NEJMcp071137 | s2cid = 42515260 }}</ref> The high pulse pressure in elderly people with hypertension or isolated systolic hypertension is explained by increased [[arterial stiffness]], which typically accompanies aging and may be exacerbated by high blood pressure.<ref>{{cite journal | vauthors = Zieman SJ, Melenovsky V, Kass DA | title = Mechanisms, pathophysiology, and therapy of arterial stiffness | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 25 | issue = 5 | pages = 932–943 | date = May 2005 | pmid = 15731494 | doi = 10.1161/01.ATV.0000160548.78317.29 | doi-access = free }}</ref>

Many mechanisms have been proposed to account for the rise in peripheral resistance in hypertension. Most evidence implicates either disturbances in the kidneys' salt and water handling (particularly abnormalities in the intrarenal [[renin–angiotensin system]])<ref>{{cite journal | vauthors = Navar LG | title = Counterpoint: Activation of the intrarenal renin-angiotensin system is the dominant contributor to systemic hypertension | journal = Journal of Applied Physiology | volume = 109 | issue = 6 | pages = 1998–2000; discussion 2015 | date = December 2010 | pmid = 21148349 | pmc = 3006411 | doi = 10.1152/japplphysiol.00182.2010a }}</ref> or abnormalities of the [[sympathetic nervous system]].<ref>{{cite journal | vauthors = Esler M, Lambert E, Schlaich M | title = Point: Chronic activation of the sympathetic nervous system is the dominant contributor to systemic hypertension | journal = Journal of Applied Physiology | volume = 109 | issue = 6 | pages = 1996–1998; discussion 2016 | date = December 2010 | pmid = 20185633 | doi = 10.1152/japplphysiol.00182.2010 | s2cid = 7685157 }}</ref> These mechanisms are not mutually exclusive and it is likely that both contribute to some extent in most cases of essential hypertension. It has also been suggested that [[endothelial dysfunction]] and vascular [[inflammation]] may also contribute to increased peripheral resistance and vascular damage in hypertension.<ref>{{cite journal | vauthors = Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S | title = Endothelium-dependent contractions and endothelial dysfunction in human hypertension | journal = British Journal of Pharmacology | volume = 157 | issue = 4 | pages = 527–536 | date = June 2009 | pmid = 19630832 | pmc = 2707964 | doi = 10.1111/j.1476-5381.2009.00240.x }}</ref><ref>{{cite journal | vauthors = Marchesi C, Paradis P, Schiffrin EL | title = Role of the renin-angiotensin system in vascular inflammation | journal = Trends in Pharmacological Sciences | volume = 29 | issue = 7 | pages = 367–374 | date = July 2008 | pmid = 18579222 | doi = 10.1016/j.tips.2008.05.003 }}</ref> [[Interleukin 17]] has garnered interest for its role in increasing the production of several other [[cytokine|immune system chemical signals]] thought to be involved in hypertension such as [[tumor necrosis factor alpha]], [[interleukin 1]], [[interleukin 6]], and [[interleukin 8]].<ref name="Gooch2014">{{cite journal | vauthors = Gooch JL, Sharma AC | title = Targeting the immune system to treat hypertension: where are we? | journal = Current Opinion in Nephrology and Hypertension | volume = 23 | issue = 5 | pages = 473–479 | date = September 2014 | pmid = 25036747 | doi = 10.1097/MNH.0000000000000052 | s2cid = 13383731 }}</ref>

Excessive [[sodium]] or insufficient [[potassium]] in the diet leads to excessive intracellular sodium, which contracts vascular smooth muscle, restricting blood flow and so increases blood pressure.<ref>{{cite journal | vauthors = Adrogué HJ, Madias NE | title = Sodium and potassium in the pathogenesis of hypertension | journal = The New England Journal of Medicine | volume = 356 | issue = 19 | pages = 1966–1978 | date = May 2007 | pmid = 17494929 | doi = 10.1056/NEJMra064486 | s2cid = 22345731 }}</ref><ref>{{cite journal | vauthors = Perez V, Chang ET | title = Sodium-to-potassium ratio and blood pressure, hypertension, and related factors | journal = Advances in Nutrition | volume = 5 | issue = 6 | pages = 712–741 | date = November 2014 | pmid = 25398734 | pmc = 4224208 | doi = 10.3945/an.114.006783 }}</ref> Non-modulating essential hypertension is a form of [[salt]]-sensitive hypertension, where [[sodium]] intake does not modulate either [[Adrenal gland|adrenal]] or [[Kidney|renal]] [[Vascular system|vascular]] responses to [[angiotensin II]].<ref>{{cite journal | vauthors = Williams GH, Hollenberg NK | title = Non-modulating essential hypertension: a subset particularly responsive to converting enzyme inhibitors | journal = Journal of Hypertension Supplement | volume = 3 | issue = 2 | pages = S81–S87 | date = November 1985 | pmid = 3003304 }}</ref> They make up 25% of the hypertensive population.<ref name="Harrison2018">{{Cite book |title=Harrison's Principles of Internal Medicine |date=2018 |publisher=McGraw-Hill Education |isbn=978-1-259-64404-7 |editor-last=Harrison |editor-first=Tinsley Randolph |edition=20th |editor-last2=Jameson |editor-first2=J. Larry |editor-last3=Fauci |editor-first3=Anthony S. |editor-last4=Kasper |editor-first4=Dennis L. |editor-last5=Hauser |editor-first5=Stephen L. |editor-last6=Longo |editor-first6=Dan L. |editor-last7=Loscalzo |editor-first7=Joseph | page = 1896 | quote = When plasma renin activity (PRA) is plotted against 24-h sodium excretion, ~10–15% of hypertensive patients have high PRA and 25% have low PRA. High-renin patients may have a vasoconstrictor form of hypertension, whereas low-renin patients may have volume-dependent hypertension. }}</ref>