Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity

Susumu Watanabe, Duk Hee Kang, Lili Feng, Takahiko Nakagawa, John Kanellis, Hui Lan, Marilda Mazzali, Richard J. Johnson

Research output: Contribution to journalReview articlepeer-review

496 Scopus citations


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.

Original languageEnglish
Pages (from-to)355-360
Number of pages6
Issue number3
StatePublished - Sep 2002


  • Hypertension, sodium-dependent
  • Mutation
  • Renal disease
  • Uric acid


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