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

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.

Dissociation of Hyperglycemia from Altered Vascular Contraction and Relaxation Mechanisms in Caveolin-1 Null Mice

“…Abnormal vascular function may play a role in obesity-related hypertension (Lastra et al, 2010). Interestingly, cav-1 may modulate the metabolic pathways in adipose cells.…”

Link between Insulin Resistance and Hypertension: What Have We Learned from Our Ancestors?

“…High salt diet impairs insulin sensitivity in hypertensive patients with salt-sensitivity but not in those with salt-resistance [1]. Clinical studies have demonstrated that salt sensitive hypertension is more prevalent among populations of patients that are obese, aging, postmenopausal, and/or manifest the metabolic syndrome [20,21].…”

“…Excess dietary salt and caloric intake, as commonly found in western diets, has been shown to promote hypertensive and metabolic diseases [1]. However, in pre-modern times, sodium deprivation threatened human survival, particularly in hot and dry climates such as the African savannah.…”

“…Obesity, physical inactivity, hypertension, hyperlipidemia and aging, which are independent risk factors for cardiovascular disease, contribute to the complex interaction between genetic and environmental factors required for impaired insulin signaling [1]. Clinical studies have shown that hypertension and insulin resistance often coexist and their association increases cardiovascular risk and the incidence of new onset type 2 diabetes [2,3].…”

Is diabetic cardiomyopathy a specific entity?

“…Activation of the renin-angiotensin-aldosterone and sympathetic system Hyperinsulinemia causes overactivation of the reninangiotensin-aldosterone system [30] . This leads to cardiac insulin resistance and the activation of mitogen activated protein kinases, which promote fibroblast proliferation while inducing cardiomyocyte fibrosis and apoptosis [31] .…”