https://orcid.org/0000-0002-7101-7331
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ABSTRACT
Aim: Marinobufagenin (MBG), a cardiotonic steroid and a natriuretic hormone, is elevated in response to high salt diet consumption. In animal models salt intake stimulates adrenocortical MBG secretion via increased angiotensin II, sympathetic activity and aldosterone. No evidence in humans exists to suggest the involvement of the angiotensinergic-sympatho-excitatory pathway in MBG production. We investigated whether MBG is related to indices of autonomic activity in men and women.
Methods: This cross-sectional study included 680 black and white, men and women from the African-PREDICT study (aged 20–30 years). Continuous 24 hr ECG recordings were used to obtain low and high frequency (LF, HF) heart rate variability (HRV). We measured 24 hr urinary MBG excretion and serum aldosterone.
Results: We found a positive association of MBG excretion with estimated salt intake (P < 0.001) and aldosterone (P < 0.001) in women and men. In women only, a positive relationship was evident between MBG excretion and LF HRV in multivariate adjusted regression analyses (Adj. R2 = 0.33; β = 0.11; P = 0.030). In men, MBG excretion associated positively with HF HRV in similar regression analyses (R2 = 0.36; β = 0.12; P = 0.034). Sex-specific results were corroborated only in blacks, namely, a positive association of MBG excretion with LF HRV in black women (R2 = 0.38; β = 0.13; P = 0.036), and negative association with HF HRV in black men (R2 = 0.40; β = 0.18; P = 0.045). No relationships were evident in white women (P = 0.58) or men (P = 0.27).
Conclusion: Our findings in this human cohort support suggested mechanisms whereby MBG is elevated as a result of increased salt intake, including autonomic activity, previously demonstrated in Dahl salt-sensitive hypertension.
Acknowledgements
The authors of this study are grateful towards all individuals participating voluntarily in the study. The dedication of the support and research staff as well as students at the Hypertension Research and Training Clinic at the North-West University is also duly acknowledged.
Disclosure statement
No potential conflict of interest was reported by the authors.
Notes on contributors
Michél Strauss is a PhD student completing her degree in Physiology at the North-West University of Potchefstroom. Her research interests are centered on a better understanding of the development of cardiovascular disease, especially in a South African population. Her current research, as part of her thesis, focuses on the novel steroidal biomarker marinobufagenin and its association with early markers of cardiovascular risk in young adults.
Wayne Smith is a Senior Lecturer within the Hypertension in Africa Research Team (HART). His earlier work was done in experimental cardiovascular physiology, but he made the move to HART in 2010 where he became involved with the research groups clinical epidemiological studies. To date, he has been involved in several epidemiological studies (The SABPA study, PURE study (South African leg), EndoAfrica and the African PREDICT study). His current research interests include (1) Static and dynamic retinal vessel analysis and its link with cardiovascular health and (2) metabolic contributions to vascular changes.
Dr Wen Wei is a Contractor Research Associate at the Laboratory of Cardiovascular Science of the National Institute on Aging (NIA), NIH (Baltimore, MD, USA) since 2009. She obtained her B.S. degree from Fudan University, Shanghai, China in 1993 with the major in Chemistry, M.S./Ph.D/ degree from Rutgers University, Newark, NJ, USA in 2003 with the major in Biochemistry. Dr Wei was enrolled in Postdoctoral fellowship program at the Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA (2003–2005) and at the Department of Physiology, School of Medicine, University of Maryland, Baltimore, MD, USA (2005–2007) in Biochemistry. Prior to her present position, she worked as a Teaching assistant and research assistant, Chemistry Department, Rutgers University, Newark, NJ, USA (1999–2003). Dr Wei is a co-author of 22 peer-reviewed publications. She provides a scientific and technical support in the current NIA/NIH/IRP projects (‘Aging and interaction of natriuretic factors on renal and vascular sodium pump’; ‘Sodium pump inhibitors in blood pressure regulation and in pro-fibrotic signaling in salt-sensitive hypertension and aging’; ‘Exploring interactions between age-associated vascular and neurodegenerative processes in cognitive impairment and Alzheimer’s disease’).
Dr Olga V. Fedorova is a Staff Scientist at the Laboratory of Cardiovascular Science of the National Institute on Aging (NIA), NIH (Baltimore, MD, USA) since 2001. She obtained her M.A. degree from State University (St. Petersburg, Russia) in 1985 with the major in Physiology and Neuroscience, and a Ph.D. degree from the Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences (St. Petersburg, Russia) in Biochemistry in 1992. Dr Fedorova was enrolled in Postdoctoral fellowship program at the NIA, NIH, Baltimore, MD, USA (1992–1997) in Biochemistry and Cardiovascular Science. Prior to her present position, she worked as a Researcher, Laboratory of Comparative Biochemistry, Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia (1985–1992); and as a Visiting Associate, Laboratory of Cardiovascular Science (LCS), NIA, NIH, Baltimore, MD, USA (1997–2001). Dr Fedorova is a member of several professional Societies including the American Heart Association/American Society of Hypertension, European/International Societies of Hypertension, and HYPERLINK “https://act.alz.org/site/SPageServer?pagename=ISTAART_homepage” \t “_blank”International Society to Advance Alzheimer's Research and Treatment. She is a co-author of 86 peer-reviewed publications, a co-investigator in two NIA/NIH/IRP projects (‘Development of therapeutic antibodies to cardiotonic steroids’; ‘Aging and interaction of natriuretic factors on renal and vascular sodium pump’), and a PI in two NIA/NIH/IRP projects (‘Sodium pump inhibitors in blood pressure regulation and in pro-fibrotic signaling in salt-sensitive hypertension and aging’; ‘Exploring interactions between age-associated vascular and neurodegenerative processes in cognitive impairment and Alzheimer’s disease’).
Aletta E. Schutte is Professor of Physiology, and the South African Research Chair (SARChI) in the Early Detection and Prevention of Cardiovascular Disease in South Africa - hosted by the Hypertension in Africa Research Team (HART) at the North-West University. She is also the Unit Director of Medical Research Council Extramural Unit for Hypertension and Cardiovascular Disease. Her research focus is the identification of early markers for the development of hypertension, and ultimately the prevention of cardiovascular disease in the black South African population. She has published over 200 papers on hypertension. She has been acknowledged for her work winning several awards, including the Distinguished Woman Scientist in the Natural, Engineering and Life Sciences award, presented by the South African Department of Science and Technology, and the AU-TWAS (African Union & The World Academy of Sciences) Award. She serves as Editor of the European Journal of Preventive Cardiology and on the Editorial Board of Hypertension, Journal of Hypertension, Journal of Clinical Hypertension, Journal of Human Hypertension, and Current Hypertension Reports. She is the immediate Past President of the Southern African Hypertension Society (SAHS); and President of the International Society of Hypertension (ISH).