Brittany Butts1, David A Calhoun2, Thomas S Denney3, Steven G Lloyd2, Himanshu Gupta4, Krishna K Gaddam2, Inmaculada Aban5, Suzanne Oparil2, Paul W Sanders6, Rakesh Patel7, James F Collawn8, Louis J Dell'Italia9. 1. Division of Cardiovascular Disease, University of Alabama at Birmingham School of Medicine, USA; Nell Hodgson Woodruff School of Nursing, Emory University, USA. 2. Division of Cardiovascular Disease, University of Alabama at Birmingham School of Medicine, USA. 3. Department of Electrical and Computer Engineering, Auburn University, USA. 4. Division of Cardiovascular Disease, University of Alabama at Birmingham School of Medicine, USA; Birmingham Department of Veterans Affairs Medical Center, USA. 5. Department of Biostatistics, University of Alabama at Birmingham, USA. 6. Division of Nephrology, University of Alabama at Birmingham School of Medicine, USA. 7. Center for Free Radical Biology and Department of Pathology, University of Alabama at Birmingham, USA. 8. Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, USA. 9. Division of Cardiovascular Disease, University of Alabama at Birmingham School of Medicine, USA; Birmingham Department of Veterans Affairs Medical Center, USA. Electronic address: louis.dellitalia@va.gov.
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.
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.
Authors: Mustafa I Ahmed; James D Gladden; Silvio H Litovsky; Steven G Lloyd; Himanshu Gupta; Seidu Inusah; Thomas Denney; Pamela Powell; David C McGiffin; Louis J Dell'Italia Journal: J Am Coll Cardiol Date: 2010-02-16 Impact factor: 24.094
Authors: Piotr Ponikowski; Adriaan A Voors; Stefan D Anker; Héctor Bueno; John G F Cleland; Andrew J S Coats; Volkmar Falk; José Ramón González-Juanatey; Veli-Pekka Harjola; Ewa A Jankowska; Mariell Jessup; Cecilia Linde; Petros Nihoyannopoulos; John T Parissis; Burkert Pieske; Jillian P Riley; Giuseppe M C Rosano; Luis M Ruilope; Frank Ruschitzka; Frans H Rutten; Peter van der Meer Journal: Rev Esp Cardiol (Engl Ed) Date: 2016-12
Authors: John J Sim; Simran K Bhandari; Jiaxiao Shi; In Lu A Liu; David A Calhoun; Elizabeth A McGlynn; Kamyar Kalantar-Zadeh; Steven J Jacobsen Journal: Mayo Clin Proc Date: 2013-10 Impact factor: 7.616
Authors: Jennifer J DuPont; Jody L Greaney; Megan M Wenner; Shannon L Lennon-Edwards; Paul W Sanders; William B Farquhar; David G Edwards Journal: J Hypertens Date: 2013-03 Impact factor: 4.844
Authors: Eduardo Pimenta; Krishna K Gaddam; Monique N Pratt-Ubunama; Mari K Nishizaka; Inmaculada Aban; Suzanne Oparil; David A Calhoun Journal: Hypertension Date: 2007-12-17 Impact factor: 10.190
Authors: Carlos M Ferrario; Leanne Groban; Hao Wang; Xuming Sun; Jessica L VonCannon; Kendra N Wright; Sarfaraz Ahmad Journal: Kidney Int Suppl (2011) Date: 2022-03-18