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Salt, aldosterone, and insulin resistance: impact on the cardiovascular system

Nature Reviews Cardiology volume 7, pages 577–584 (2010)Cite this article

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Abstract

Hypertension and type 2 diabetes mellitus (T2DM) are powerful risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD), both of which are leading causes of morbidity and mortality worldwide. Research into the pathophysiology of CVD and CKD risk factors has identified salt sensitivity and insulin resistance as key elements underlying the relationship between hypertension and T2DM. Excess dietary salt and caloric intake, as commonly found in westernized diets, is linked not only to increased blood pressure, but also to defective insulin sensitivity and impaired glucose homeostasis. In this setting, activation of the sympathetic nervous system and the renin–angiotensin–aldosterone system (RAAS), as well as increased signaling through the mineralocorticoid receptor (MR), result in increased production of reactive oxygen species and oxidative stress, which in turn contribute to insulin resistance and impaired vascular function. In addition, insulin resistance is not limited to classic insulin-sensitive tissues such as skeletal muscle, but it also affects the cardiovascular system, where it participates in the development of CVD and CKD. Current clinical knowledge points towards an impact of salt restriction, RAAS blockade, and MR antagonism on cardiovascular and renal protection, but also on improved insulin sensitivity and glucose homeostasis.

Key Points

  • A pathophysiological link exists between hypertension and insulin resistance

  • Excess dietary salt intake has been linked to activation of the sympathetic nervous system (SNS), decreased insulin sensitivity, and activation of the renin–angiotensin–aldosterone system (RAAS)

  • SNS and RAAS activation and decreased insulin sensitivity participate in the pathogenesis of vascular dysfunction, which seems to be mediated by increased inflammation and oxidative stress

  • Insulin resistance affects classic insulin target tissues such as skeletal muscle, but also cardiovascular and renal tissue where it contributes to the development of cardiovascular and chronic kidney disease

  • Current studies suggest a beneficial role of mineralocorticoid receptor blockade, RAAS modulation, and decreased sodium intake on hypertension, insulin resistance, and cardiovascular and renal diseases

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Figure 1: Genomic and nongenomic actions of aldosterone and interaction with the mineralocorticoid receptor.

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  1. Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Missouri School of Medicine, D109 HSC Diabetes Center, One Hospital Drive, Columbia, 65212, MO, USA

    Guido Lastra, Megan S. Johnson & James R. Sowers

  2. Division of General Internal Medicine, Department of Internal Medicine, University of Missouri School of Medicine, D109 HSC Diabetes Center, One Hospital Drive, Columbia, 65212, MO, USA

    Sonal Dhuper

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G. Lastra, S. Dhuper, M. S. Johnson, and J. R. Sowers contributed to discussion of content for the article, researched data to include in the manuscript, reviewed and edited the manuscript before submission, and revised the manuscript in response to the peer-reviewers' comments.

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Correspondence to James R. Sowers.

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Lastra, G., Dhuper, S., Johnson, M. et al. Salt, aldosterone, and insulin resistance: impact on the cardiovascular system. Nat Rev Cardiol 7, 577–584 (2010). https://doi.org/10.1038/nrcardio.2010.123

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