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. 2019 Apr:134:343-349.
doi: 10.1016/j.freeradbiomed.2019.01.029. Epub 2019 Jan 26.

Plasma xanthine oxidase activity is related to increased sodium and left ventricular hypertrophy in resistant hypertension

Brittany Butts  1 , David A Calhoun  2 , Thomas S Denney Jr  3 , Steven G Lloyd  2 , Himanshu Gupta  4 , Krishna K Gaddam  2 , Inmaculada Aban  5 , Suzanne Oparil  2 , Paul W Sanders  6 , Rakesh Patel  7 , James F Collawn  8 , Louis J Dell'Italia  9
Affiliations

Plasma xanthine oxidase activity is related to increased sodium and left ventricular hypertrophy in resistant hypertension

Brittany Butts et al. Free Radic Biol Med. 2019 Apr.

Abstract

Background: The extra-renal effects of aldosterone on left ventricular (LV) structure and function are exacerbated by increased dietary sodium in persons with hypertension. Previous studies demonstrated endothelial dysfunction and increased oxidative stress with high salt diet in normotensive salt-resistant subjects. We hypothesized that increased xanthine oxidase (XO), a product of endothelial cells, is related to 24-h urinary sodium and to LV hypertrophy and function in patients with resistant hypertension (RHTN).

Methods: The study group included persons with RHTN (n = 91), defined as a blood pressure > 140/90 mmHg on ≥ 3 medications at pharmacologically effective doses. Plasma XO activity and 24-h urine were collected, and cardiac magnetic resonance imaging (MRI) was performed to assess LV function and morphology. Sixty-seven normotensive persons on no cardiovascular medications served as controls. A subset of RHTN (n = 19) received spironolactone without salt restriction for six months with follow-up XO activity measurements and MRI analyses.

Results: XO activity was increased two-fold in RHTN vs. normal and was positively correlated with LV mass, LV diastolic function, and 24-h urinary sodium. In RHTN patients receiving spironolactone without salt restriction, LV mass decreased, but LV diastolic function and XO activity did not improve. Baseline urinary sodium was positively associated with rate of change of LV mass to volume ratio and the LV E/A ratio.

Conclusions: These results demonstrate a potential role of endothelium-derived oxidative stress and excess dietary salt in the pathophysiology of LV hypertrophy and diastolic dysfunction in persons with RHTN unaffected by the addition of spironolactone.

Keywords: Dietary sodium; Left ventricular hypertrophy; Oxidative stress; Xanthine oxidase.

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Figures

Figure 1.
Figure 1.
Representative left ventricular (LV) volume-time curve in resistant hypertension (RHTN) and normotensive control (NC). The decrease in the slope of the passive diastolic LV filling phase and the accentuated slope in the late active phase demonstrate impaired LV diastolic function in RHTN as compared to NC.
Figure 2.
Figure 2.
Cardiac MRI images of a 53-year-old male normotensive control (left column) and a 53-year-old male resistant hypertension (right column). Top row: short-axis view at end diastole. Bottom row: 2-chamber view at end diastole. These images demonstrate the increased wall thickness and end diastolic volume of our patients with resistant hypertension. This represents a dilated concentric pattern of hypertrophy, manifested by increased mass to volume ratio and decreased radius to wall thickness ratio.
Figure 3.
Figure 3.
Linear relationships between left ventricular (LV) diastolic mass and volume and urinary aldosterone and sodium in persons with resistant hypertension (n=91). Partial correlation (r) values are adjusted for age, gender, and BMI. The shaded area represents 95% confidence interval of the mean.
Figure 4.
Figure 4.
Plasma xanthine oxidase activity is related to 24-hour urinary sodium, left ventricular end-diastolic mass, and normalized peak early diastolic filling rate in persons with resistant hypertension (n=91). Partial correlation (r) values are adjusted for age, gender, and BMI. Xanthine oxidase values were log transformed for better visualization of the data.
See this image and copyright information in PMC

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