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Serum uric acid, the endothelium and hypertension: an association revisited

Journal of Human Hypertension volume 21, pages 591–593 (2007)Cite this article

Humans developed elevated uric acid because of several mutations in the urate oxidase (uricase) gene that render it non-functional.1 These occurred during the Miocene Era, some 18–22 million years ago. The first mutation is likely to have occurred when the Pongo (orangutan)/Gorilla/Pan (chimpanzee)/Homo (human) line split from other apes. Gibbons and Siamangs therefore do not have mutated uricase. The second and third mutations occurred after the Pongo line separated off. It has been proposed that the mutation was retained because it offered survival benefits. Is this plausible?

One suggestion has been that the antioxidant properties of urate were protective. An alternative view is that urate regulates blood pressure and improves the animals’ ability to maintain blood pressure in low salt environments.1 In rats, inhibition of uricase with oxonic acid causes hyperuricaemia. If these rats are given a low-salt diet, their blood pressure increases owing to stimulation of the renin–angiotensin system. Thus, one would expect that humans with higher uric acid levels would be likely to develop higher blood pressure. The Framingham study data set has been used to demonstrate just this fact: that having elevated uric acid is a risk factor for future development of hypertension,2 so it is possible that this theory holds water, or perhaps sodium, given the relationship of the latter to hypertension.

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References

  1. Watanabe S, Kang D-H, Feng L, Nakagawa T, Kanellis J, Lan H et al. Uric acid, hominod evolution, and the pathogenesis of salt sensitivity. Hypertension 2002; 40: 355–360.

    Article  CAS  Google Scholar 

  2. Sundstrom J, Sullivan L, D’Agostino RB, Levy D, Kannel WB, Vasan RS . Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension 2005; 45: 28–33.

    Article  Google Scholar 

  3. Hayden MR, Tyagi SC . Uric acid: a new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type II diabetes mellitus: the urate redox shuttle. Nutr & Metab 2004; 1: 10 doi 10.1186/1743-7075-1-10. http://www.nutritionandmetabolism.com/content/1/1/10.

    Article  Google Scholar 

  4. Hansen TW, Jeppesen J, Rasmussen S, Ibsen H, Torp-Pedersen C . Ambulatory blood pressure and mortality: a population based study. Hypertension 2005; 45: 499–504.

    Article  CAS  Google Scholar 

  5. Stepnowsky CJ, Nelesen RA, DeJardin D, Dimsdale JE . Socioeconomic status is associated with nocturnal blood pressure dipping. Psychosom Med 2004; 66: 651–655.

    Article  Google Scholar 

  6. Ichihara A, Kaneshiro Y, Sakoda M, Hayashi M . Ambulatory blood pressure variability and brachial pulse wave velocity in untreated hypertensive patients. J Hum Hypertens 2006; 20: 529–536.

    Article  CAS  Google Scholar 

  7. Henskens LH, Kroon AA, Hofman PA, Gronenschild EH, Jolles J, de Leeuw PW, VAN boXTEL mp. Ambulatory blood pressure, asymptomatic cerebrovascular damage and cognitive function in essential hypertension. J Hum Hypertens 2006; 20: 5–13.

    Article  Google Scholar 

  8. Kotsis V, Stabouli S, Pitiraga V, Papamichael C, Toumanidis S, Zakopoulos N . Impact of gender on 24-h ambulatory blood pressure and target organ damage. J Hum Hypertens 2006; 20: 658–665.

    Article  CAS  Google Scholar 

  9. Verdecchia P, Schillaci G, Reboldi G, Santeusanio F, Porcellati C, Branetti P . Relation between serum uric acid and risk of cardiovascular disease in essential hypertension: The PIUMA study. Hypertension 2000; 36: 1072–1078.

    Article  CAS  Google Scholar 

  10. Weir CJ, Muir SW, Walters MR, Lees KR . Serum urate as an independent predictor of poor outcome and future vascular events after acute stroke. Stroke 2003; 34: 1951–1957.

    Article  Google Scholar 

  11. Matsumara K, Ohtsubo T, Oniki H, Fujii K, Iida M . Gender-related association of serum uric acid and left ventricular hypertrophy in hypertension. Circ J 2006; 70: 885–888.

    Article  Google Scholar 

  12. Perlstein TS, Gumieniak O, Williams GH, Sparrow D, Vokonas PS, Gaziano M et al. Uric acid and the development of hypertension: the normative aging study. Hypertension 2006; 48: 1031–1036.

    Article  CAS  Google Scholar 

  13. Feig DI, Mazzali M, Kang DH, Nakagawa T, Price K, Kannelis J et al. Serum uric acid: a risk factor and a target for treatment? J Am Soc Nephrol 2006; 17 (4 suppl 2): S69–S73.

    Article  CAS  Google Scholar 

  14. Mancia G, Parati G, Borghi C, Ghironzi G, Andriani E, Marinelli L et al. Hypertension prevalence, awareness, control and association with metabolic abnormalities in the San Marino population: the SMOOTH Trial. J Hypertens 2006; 24: 837–843.

    Article  CAS  Google Scholar 

  15. Tsouli SG, Liberopoulos EN, Mikhailidis DP, Athyros VG, Elisaf MS . Elevated serum uric acid levels in metabolic syndrome: an acive component or an innocent bystander. Metab: Clin Exp 2006; 55: 1293–1301.

    Article  CAS  Google Scholar 

  16. Onat A, Uyarel H, Hergenc G, Karabulat A, Albayrak S, Sari I et al. Serum uric acid is a determinant of metabolic syndrome in a population-based study. Am J Hypertens 2006; 19: 1055–1062.

    Article  CAS  Google Scholar 

  17. Coutinho T, Turner ST, Kullo IJ . Serum uric acid is associated with microvascular function in hypertensive individuals. J Human Hypertens [E-pub ahead of print: 31 May 2007; doi:10.1038/sj.jhh.1002193].

  18. Kato M, Hisatome I, Tomikura Y, Kotani K, Kinugawa T, Ogino K et al. Status of endothelial dependent vasodilation in patiemnts with hyperuricaemia. Am J Cardiol 2005; 96: 1576–1578.

    Article  CAS  Google Scholar 

  19. Mercuro G, Vitale C, Cerquetani E, Zoncu S, Deidda M, Fini M et al. Hormonal and cytokine effects of uric acid. Curr Opin Hypertens 2006; 15: 30–33.

    Article  Google Scholar 

  20. Hermida RC, Ayala DE, Calvo C, López JE, Mojón A, Fontao MJ et al. Effects of time of day of treatment on ambulatory blood pressure pattern of patients with resistant hypertension. Hypertension 2005; 46: 1053–1059.

    Article  CAS  Google Scholar 

  21. Cuspidi C, Meani S, Fusi V, Severgnini B, Valerio C, Catini E et al. Is the nocturnal fall in blood pressure reduced in essential hypertensive patients with metabolic syndrome? Blood Press 2004; 13: 230–235.

    Article  Google Scholar 

  22. Tartan Z, Uyarel H, Kasikcioglu H, Alper AT, Ozay B, Bilsel T et al. Metabolic syndrome as a predictor of non-dipping hypertension. Tohoku J Exp Med 2006; 210: 57–66.

    Article  Google Scholar 

  23. JBS 2. Joint British Societies’ guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005; 91: 1–52.

    Article  Google Scholar 

  24. The DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006; 368: 1096–1105.

    Article  Google Scholar 

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  1. Clinical Chemistry Department, Queen's Hospital, Burton-on-Trent, Staffordshire, UK

    T Reynolds

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Reynolds, T. Serum uric acid, the endothelium and hypertension: an association revisited. J Hum Hypertens 21, 591–593 (2007). https://doi.org/10.1038/sj.jhh.1002239

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