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Short\u2010term and long\u2010term BP regulation involve the integrated actions of multiple cardiovascular, renal, neural, endocrine, and local tissue control systems. Clinical and experimental observations strongly support a central role for the kidneys in the long\u2010term regulation of BP, and abnormal renal\u2010pressure natriuresis is present in all forms of chronic hypertension. Impaired renal\u2010pressure natriuresis and chronic hypertension can be caused by<jats:italic>intrarenal<\/jats:italic>or<jats:italic>extrarenal<\/jats:italic>factors that reduce glomerular filtration rate or increase renal tubular reabsorption of salt and water; these factors include excessive activation of the renin\u2010angiotensin\u2010aldosterone and sympathetic nervous systems, increased formation of reactive oxygen species, endothelin, and inflammatory cytokines, or decreased synthesis of nitric oxide and various natriuretic factors. In human primary (essential) hypertension, the precise causes of impaired renal function are not completely understood, although excessive weight gain and dietary factors appear to play a major role since hypertension is rare in nonobese hunter\u2010gathers living in nonindustrialized societies. Recent advances in genetics offer opportunities to discover gene\u2010environment interactions that may also contribute to hypertension, although success thus far has been limited mainly to identification of rare monogenic forms of hypertension. \u00a9 2012 American Physiological Society.<jats:italic>Compr Physiol<\/jats:italic>2:2393\u20102442, 2012.<\/jats:p>","DOI":"10.1002\/cphy.c110058","type":"other","created":{"date-parts":[[2012,9,19]],"date-time":"2012-09-19T13:16:56Z","timestamp":1348060616000},"page":"2393-2442","source":"Crossref","is-referenced-by-count":166,"title":["Hypertension: Physiology and Pathophysiology"],"prefix":"10.1002","author":[{"given":"John E.","family":"Hall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joey P.","family":"Granger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussara M.","family":"do Carmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre A.","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Dubinion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shereen","family":"Hamza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Speed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.19.2486"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.38.3.379"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.090894"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192644"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2006.01858.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(01)02255-5"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.2.485"},{"key":"e_1_2_10_10_1","unstructured":"AlexanderJ DustanHP SimsEAH TaraziR. 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