on July 29, 2002
Hypertension. 2002
Published online before print July 29, 2002, doi: 10.1161/01.HYP.0000028589.66335.AA
Published online before print July 29, 2002, doi: 10.1161/01.HYP.0000028589.66335.AA
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Submitted on February 12, 2002
From the Division of Nephrology, Baylor College of Medicine, Houston, Tex. * To whom correspondence should be addressed. E-mail: rjohnson{at}bcm.tmc.edu.
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.
Revised on March 20, 2002
Uric Acid, Hominoid Evolution, and the Pathogenesis of Salt-Sensitivity
Susumu Watanabe;
Key words: uric acid • hypertension, sodium-dependent • renal disease • mutation
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