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

Abstract

BACKGROUND\nThe 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).\n\n\nMETHODS\nThe study group included persons with RHTN (n\u202f=\u202f91), defined as a blood pressure\u202f>\u202f140/90\u202fmmHg on\u202f≥\u202f3 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\u202f=\u202f19) received spironolactone without salt restriction for six months with follow-up XO activity measurements and MRI analyses.\n\n\nRESULTS\nXO 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.\n\n\nCONCLUSIONS\nThese 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.