Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity.
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.
Watanabe
Susumu
S
Division of Nephrology, Baylor College of Medicine, Houston, Tex 77030, USA.
Kang
Duk-Hee
DH
Feng
Lili
L
Nakagawa
Takahiko
T
Kanellis
John
J
Lan
Hui
H
Mazzali
Marilda
M
Johnson
Richard J
RJ
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
D017673:Sodium Chloride, Dietary; D014527:Uric Acid; D014503:Urate Oxidase