What are the key arguments against uric acid as a true risk factor for hypertension?

Academic Article

Abstract

  • Koch's postulates have been satisfied for the uric acid-hypertension relation, but there are still important questions to be addressed before completly accepting hyperuricemic hypertension as a clinical entity. In addition to resolving the key arguments against the uric acid hypothesis (see above), we need more studies to address the ends of the spectrum in the uric acid-hypertension pathway, by both identifying the intracellular mechanisms of action of how uric acid might induce intracellular oxidative stress, as well as definitive clinical trials in larger populations to assess the benefit of lowering uric acid in high blood pressure. We need to determine whether the benefits of lowering uric acid are primarily mediated by the inhibition of the renin angiotensin system, as suggested by some experimental22,36,37 and clinical studies,38 or whether it involves effects beyond the renin angiotensin system.39 The role of xanthine oxidase-induced oxidants needs further study. Some studies suggest that both uric acid and oxidants induced by xanthine oxidase may drive inflammation,40 whereas under other conditions the suppressive effects of xanthine oxidase inhibition on cell metabolism can be reversed by adding back uric acid.41 Integrating the uric acid story with current theories of the cause of hypertension is also important. An elevated uric acid is now recognized as a feature in low birth weight infants and is associated with endothelial dysfunction and the future development of hypertension.1 The uric acid pathway may also be important in obesity-associated hypertension, as uric acid has profound effects on adipocytes and adipokines, including adiponectin and leptin,42-44 as leptin is emerging as a key mediator in this condition.45 The observation that mitochondrial oxidants have a role in hypertension46 is also consistent with recent studies in the hyperuricemia model.24 Finally, the emerging role of intrarenal T cells in driving salt-sensitive hypertension47-50 is supported by the finding that chronic hyperuricemia in animals leads to salt-sensitive hypertension in association with tubulointerstititial inflammation and microvascular disease.2 In conclusion, multiple questions about the role of uric acid in blood pressure remain. Nevertheless, we predict that hyperuricemic hypertension will one day be recognized as a clinical entity. © 2013 American Heart Association, Inc.
  • Authors

    Published In

  • Hypertension  Journal
  • Digital Object Identifier (doi)

    Author List

  • Johnson RJ; Sánchez-Lozada LG; Mazzali M; Feig DI; Kanbay M; Sautin YY
  • Start Page

  • 948
  • End Page

  • 951
  • Volume

  • 61
  • Issue

  • 5