Document Detail

Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity.
MedLine Citation:
PMID:  12215479     Owner:  NLM     Status:  MEDLINE    
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.
Susumu Watanabe; Duk-Hee Kang; Lili Feng; Takahiko Nakagawa; John Kanellis; Hui Lan; Marilda Mazzali; Richard J Johnson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  40     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-09-06     Completed Date:  2002-09-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  355-60     Citation Subset:  IM    
Division of Nephrology, Baylor College of Medicine, Houston, Tex 77030, USA.
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MeSH Terms
Blood Pressure*
Cardiovascular Diseases / etiology
Cell Division
Cells, Cultured
Developed Countries
Evolution, Molecular*
Hypertension / etiology
Kidney Diseases / etiology
Models, Cardiovascular*
Muscle, Smooth, Vascular / cytology,  drug effects
Rats, Sprague-Dawley
Sodium Chloride, Dietary*
Urate Oxidase / genetics
Uric Acid / blood*,  pharmacology
Grant Support
Reg. No./Substance:
0/Sodium Chloride, Dietary; 69-93-2/Uric Acid; EC Oxidase

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