title: Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity.
abstract: Humans have elevated serum uric acid as a result of a mutation in the urate oxidase (uricase) gene that occurred during the Miocene. We hypothesize that the mutation provided a survival advantage because of the ability of hyperuricemia to maintain blood pressure under low-salt dietary conditions, such as prevailed during that period. Mild hyperuricemia in rats acutely increases blood pressure by a renin-dependent mechanism that is most manifest under low-salt dietary conditions. Chronic hyperuricemia also causes salt sensitivity, in part by inducing preglomerular vascular disease. The vascular disease is mediated in part by uric acid-induced smooth muscle cell proliferation with activation of mitogen-activated protein kinases and stimulation of cyclooxygenase-2 and platelet-derived growth factor. Although it provided a survival advantage to early hominoids, hyperuricemia may have a major role in the current cardiovascular disease epidemic.
authors.affiliation: Division of Nephrology, Baylor College of Medicine, Houston, Tex 77030, USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Watanabe
authors.forename: Duk-Hee
authors.initials: DH
authors.lastname: Kang
authors.forename: Lili
authors.initials: L
authors.lastname: Feng
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakagawa
authors.forename: John
authors.initials: J
authors.lastname: Kanellis
authors.forename: Hui
authors.initials: H
authors.lastname: Lan
authors.forename: Marilda
authors.initials: M
authors.lastname: Mazzali
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology; D002455:Cell Division; D002478:Cells, Cultured; D019049:Developed Countries; D019143:Evolution, Molecular; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007674:Kidney Diseases / Q000209:etiology; D007700:Kinetics; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D009154:Mutation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary; D014503:Urate Oxidase / Q000235:genetics; D014527:Uric Acid / Q000097:blood* / Q000494:pharmacology
chemical_list: D017673:Sodium Chloride, Dietary; D014527:Uric Acid; D014503:Urate Oxidase