Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry - PubMed (original) (raw)

Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry

Shio Yoshida et al. Sci Rep. 2020.

Abstract

Xanthine oxidoreductase (XOR) inhibitor administration reduces uric acid and reactive oxygen species (ROS) production, and also lowers blood pressure (BP). However, the associations of plasma XOR activity, uric acid level, and oxidative stress levels with BP remain unclear. This cross-sectional study included 156 subjects (68 males, 88 females) registered in the MedCity21 health examination registry without anti-hypertensive or anti-hyperuricemic agent administration. Plasma XOR activity was measured using our highly sensitive novel assay, which is unaffected by uric acid in the sample. BP was also determined, and serum uric acid and derivative of reactive oxygen metabolites (d-ROMs) levels were simultaneously measured. Median plasma XOR activity, serum uric acid, d-ROMs, and mean arterial pressure (MAP) values were 25.7 pmol/h/mL, 5.4 mg/dL, 305 Carr U, and 89.0 mmHg, respectively. Multiple regression analysis showed that plasma XOR activity (β = 0.211, p = 0.019), but not serum uric acid (β = 0.072, p = 0.502), was significantly associated with MAP. In subjects with lower but not higher d-ROMs level, an independent association of plasma XOR activity with MAP was observed (β = 0.428, p = 0.001 and β = 0.019, p = 0.891, respectively; p for interaction = 0.046). XOR may contribute to the pathophysiology of higher BP through ROS but not uric acid production, especially in patients with lower oxidative stress.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1

Plasma XOR activity independently associated with MAP in entire cohort. The best fitted line and 95% confidence interval are shown by a solid line and gray band, respectively. MAP was adjusted to the median values for age (53 years), gender (female), VFA (57.7 m2), smoking habit (absence), HbA1c (5.6%), eGFR (77.6 mL/min/1.73 m2), ARR (130.2), and uric acid level (5.4 mg/dL). Abbreviations: XOR, xanthine oxidoreductase; MAP, mean arterial pressure; VFA, visceral fat area; HbA1c, glycated hemoglobin A1c; eGFR, estimated glomerular filtration rate; ARR, aldosterone-to-renin ratio.

Figure 2

Significant association of plasma XOR activity with MAP in subjects with lower but not higher oxidative stress level. Plasma XOR activity was independently associated with MAP in subjects with a lower d-ROMs level (median <305 Carr U), but not in those with a higher d-ROMs level (median ≥305 Carr U). The best fitted line and 95% confidence interval are shown by a solid line and dark gray band, respectively. MAP was adjusted to the median values for age, gender, VFA, smoking habit, HbA1c, eGFR, ARR, and uric acid level after dividing the subjects based on lower and higher d-ROMs level. Abbreviations: XOR, xanthine oxidoreductase; MAP, mean arterial pressure; d-ROMs, derivative of reactive oxygen metabolites; VFA, visceral fat area; HbA1c, glycated hemoglobin A1c; eGFR, estimated glomerular filtration rate; ARR, aldosterone-to-renin ratio.

References

1. Hille R, Nishino T. Flavoprotein structure and mechanism. 4. Xanthine oxidase and xanthine dehydrogenase. FASEB J. 1995;9:995–1003. doi: 10.1096/fasebj.9.11.7649415. - DOI - PubMed
1. Battelli MG, Polito L, Bolognesi A. Xanthine oxidoreductase in atherosclerosis pathogenesis: not only oxidative stress. Atherosclerosis. 2014;237:562–567. doi: 10.1016/j.atherosclerosis.2014.10.006. - DOI - PubMed
1. Radi R, Rubbo H, Bush K, Freeman BA. Xanthine oxidase binding to glycosaminoglycans: kinetics and superoxide dismutase interactions of immobilized xanthine oxidase-heparin complexes. Arch Biochem Biophys. 1997;339:125–135. doi: 10.1006/abbi.1996.9844. - DOI - PubMed
1. Tan S, et al. Xanthine oxidase activity in the circulation of rats following hemorrhagic shock. Free Radic Biol Med. 1993;15:407–414. doi: 10.1016/0891-5849(93)90040-2. - DOI - PubMed
1. Houston M, et al. Binding of xanthine oxidase to vascular endothelium. Kinetic characterization and oxidative impairment of nitric oxide-dependent signaling. J Biol Chem. 1999;274:4985–4994. doi: 10.1074/jbc.274.8.4985. - DOI - PubMed

Association of plasma xanthine oxidoreductase activity with blood pressure affected by oxidative stress level: MedCity21 health examination registry - PubMed (original) (raw)