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Certain risk factors are apparent, including genetic polymorphisms that regulate sodium excretion, a congenital reduction in nephron number, obesity and hyperleptinemia, an elevated sympathetic nervous system, diet (salt and fructose), and metabolic (hyperuricemia) mechanisms. The kidney shows evidence for renal arteriolar vasoconstriction, an intrarenal inflammatory response, local oxidative stress, and intrarenal activation of the renin-angiotensin system. Recent studies suggest that intrarenal T cells have an important role in causing hypertension to be persistent, likely due to the induction of a local autoimmune response to neoantigens such as heat shock protein 70 and protein aggregates formed by isoketals resulting from lipid peroxidation. Salt retention due to impairment in pressure-diuresis leads to the release of cardiotonic steroids and central nervous system effects that cause systemic vasoconstriction and a rise in blood pressure. Some recent studies suggest that salt may increase blood pressure not simply by effects on extracellular volume but rather as a consequence of hyperosmolarity. These new insights could lead to new approaches for the prevention and treatment of this important disease.<\/jats:p>","DOI":"10.1152\/ajprenal.00503.2014","type":"journal-article","created":{"date-parts":[[2014,11,7]],"date-time":"2014-11-07T06:55:13Z","timestamp":1415343313000},"page":"F167-F178","source":"Crossref","is-referenced-by-count":43,"title":["The discovery of hypertension: evolving views on the role of the kidneys, and current hot topics"],"prefix":"10.1152","volume":"308","author":[{"given":"Richard J.","family":"Johnson","sequence":"first","affiliation":[{"name":"Division of Renal Diseases and Hypertension, University of Colorado, Denver, Colorado;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Lanaspa","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases and Hypertension, University of Colorado, Denver, Colorado;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Gabriela 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