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The renin–angiotensin–aldosterone system and calcium-regulatory hormones

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Abstract

There is increasing evidence of a clinically relevant interplay between the renin–angiotensin–aldosterone system and calcium-regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis, while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies and provide insight into the results of prior and ongoing intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent.

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Acknowledgements

The work in this publication was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health under award numbers: K23 HL11177 (to AV). Research was also supported by a Brigham and Women’s Hospital Biomedical Research Institute Grant (to AV), a William Randolph Hearst Young Investigator Award from the Brigham and Women’s Hospital Department of Medicine (to AV) and a Harvard Medical School Research Fellowship (to JMB). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

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Vaidya, A., Brown, J. & Williams, J. The renin–angiotensin–aldosterone system and calcium-regulatory hormones. J Hum Hypertens 29, 515–521 (2015). https://doi.org/10.1038/jhh.2014.125

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