Salt, aldosterone, and insulin resistance: impact on the cardiovascular system.
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.
Lastra
Guido
G
Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Missouri School of Medicine, D109 HSC Diabetes Center, One Hospital Drive, Columbia, MO 65212, USA.
Dhuper
Sonal
S
Johnson
Megan S
MS
Sowers
James R
JR
D000450:Aldosterone / Q000494:pharmacology* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000473:pathology* / Q000517:prevention & control; D002319:Cardiovascular System / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007333:Insulin Resistance; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000517:prevention & control; D008901:Mineralocorticoids / Q000494:pharmacology / Q000502:physiology; D009765:Obesity / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors; D015398:Signal Transduction; D012982:Sodium, Dietary / Q000009:adverse effects* / Q000494:pharmacology; D013564:Sympathetic Nervous System
D008901:Mineralocorticoids; D017382:Reactive Oxygen Species; D012982:Sodium, Dietary; D000450:Aldosterone