Hyperuricemia induces endothelial dysfunction

Khosla, Uday M.; Zharikov, Sergey; Finch, Jennifer L.; Nakagawa, Takahiko; Roncal, Carmen; Mu, Wei; Krotova, Karina; Block, Edward R.; Prabhakar, Sharma; Johnson, Richard J.

doi:10.1111/j.1523-1755.2005.00273.x

Cited by 1,061 publications

(833 citation statements)

References 10 publications

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“…[16][17][18] UA potently decreases endothelial nitric oxide bioavailability and induces endothelial dysfunction. 33 Elevated SUA levels were also associated with the increased generation of free radicals 34 and oxidative stress, which could abolish endothelium-dependent vasodilatation, leading to hypertension. 35 However, other studies have suggested that UA was an effective antioxidant, 36,37 and the exact role of UA in oxidation (pro-oxidant or antioxidant) remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan

et al. 2014

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The purpose of this study was to examine the associations between serum uric acid (SUA) levels and the incidences of hypertension and metabolic syndrome (MetS) in a large screened cohort of Japanese men and women. We evaluated 4812 subjects (males, 2528; females, 2284; mean age, 47.5 years) who underwent health checkups between 2006 and 2010 and were free of hypertension and MetS in 2006. After 4 years, 618 (13%), 764 (16%) and 158 (3%) subjects developed hypertension, MetS and hypertension with MetS, respectively. Increased SUA levels were significantly and positively associated with the incidences of hypertension, MetS and hypertension with MetS. Compared with the first quartile of SUA levels, the odds ratios (95% confidence intervals) for the third and fourth quartiles, respectively, were as follows: 1.5 (1.1-2.1; P = 0.0128) and 1.8 (1.2-2.5; P = 0.0022) for hypertension, 1.3 (0.9-1.9; P = 0.1910) and 1.8 (1.2-2.7; P = 0.0039) for MetS and 2.7 (1.1-6.6; P = 0.0276) and 3.2 (1.3-8.0; P = 0.0115) for hypertension with MetS. In conclusion, increased SUA levels were significantly and independently associated with the incidences of hypertension and MetS in subjects without hypertension or MetS at baseline. Increased SUA levels might also be correlated with the incidence of hypertension with MetS.

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Section: Discussionmentioning

confidence: 99%

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan

et al. 2014

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“…The consequent increase in plasma uric acid was indeed associated with a decrease in plasma nitrites/nitrates (NOx). Similarly, direct exposure of endothelial cells to uric acid slightly reduces basal or VEGF-stimulated NO production (40). Thus, uric acid can dose-dependently reduce NO bioavailability.…”

Section: Uric Acid: Antioxidant or Pro-oxidant?mentioning

confidence: 96%

Uric acid transport and disease

Thorens²

2010

J. Clin. Invest.

669

496

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Uric acid is the metabolic end product of purine metabolism in humans. It has antioxidant properties that may be protective but can also be pro-oxidant, depending on its chemical microenvironment. Hyperuricemia predisposes to disease through the formation of urate crystals that cause gout, but hyperuricemia, independent of crystal formation, has also been linked with hypertension, atherosclerosis, insulin resistance, and diabetes. We discuss here the biology of urate metabolism and its role in disease. We also cover the genetics of urate transport, including URAT1, and recent studies identifying SLC2A9, which encodes the glucose transporter family isoform Glut9, as a major determinant of plasma uric acid levels and of gout development.Conflict of interest: Alexander So has acted as a consultant and advisor for Novartis.Citation for this article:

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“…5,13,14,50 It has been suggested that hyperuricemia inhibits nitric oxide availability and decreases insulin-mediated glucose uptake in skeletal muscle and may, therefore, have a role in the development of the metabolic syndrome. 51,52 Other studies have suggested that hyperinsulinemia, a consequence of the metabolic syndrome, enhances the tubular reabsorption of uric acid and that this occurs concurrently with a decrease in sodium and potassium excretion, leading to elevated BP. 53 In both instances, the association between abdominal obesity and high BP is mediated by hyperinsulinemia, 16 which is consistent with the notion of a common exposure to hyperinsulinemia (and obesity) in the relation between SUA and BP.…”

Section: Discussionmentioning

confidence: 99%

Impact of different adiposity measures on the relation between serum uric acid and blood pressure in young adults

et al. 2011

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Serum uric acid (SUA) concentration is independently associated with blood pressure (BP) in adults. We examined this association in young adults at an age where anti-hypertension treatment, other potential confounding factors and co-morbidity are unlikely to occur. We assessed BP, anthropometric variables including weight, height, waist circumference (WC), body fat percent (using bioimpedance), lifestyle behaviors, SUA and blood lipids in 549 participants aged 19-20 years from a population-based cohort study (Seychelles Child Development Study). Mean (s.d.) SUA was higher in males than females, 0.33 (0.08) and 0.24 (0.07) mmol l À1 , respectively. Body mass index (BMI) was higher in females than males but BP was markedly higher in males than in females. SUA was associated with both systolic and diastolic BP. However, the magnitude of the linear regression coefficients relating BP and SUA decreased by up to 50% upon adjustment for BMI, WC or body fat percent. The association between SUA and BP was not altered upon further adjustment for alcohol intake, smoking, triglycerides or renal function. In fully adjusted models, SUA remained associated with BP (Po0.05) in females. In conclusion, adiposity substantially decreased the association between SUA and BP in young adults, and BP was independently associated with SUA in females. These findings suggest a role of adiposity in the link between hyperuricemia and hypertension.

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Hyperuricemia induces endothelial dysfunction

Cited by 1,061 publications

References 10 publications

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan

Associations between serum uric acid levels and the incidence of hypertension and metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan

Uric acid transport and disease

Impact of different adiposity measures on the relation between serum uric acid and blood pressure in young adults

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