The pathophysiology of hypertension in patients with obesity

Abstract

The combination of obesity and hypertension is associated with high morbidity and mortality because it leads to cardiovascular and kidney disease. Potential mechanisms linking obesity to hypertension include dietary factors, metabolic, endothelial and vascular dysfunction, neuroendocrine imbalances, sodium retention, glomerular hyperfiltration, proteinuria, and maladaptive immune and inflammatory responses. Visceral adipose tissue also becomes resistant to insulin and leptin and is the site of altered secretion of molecules and hormones such as adiponectin, leptin, resistin, TNF and IL-6, which exacerbate obesity-associated cardiovascular disease. Accumulating evidence also suggests that the gut microbiome is important for modulating these mechanisms. Uric acid and altered incretin or dipeptidyl peptidase 4 activity further contribute to the development of hypertension in obesity. The pathophysiology of obesity-related hypertension is especially relevant to premenopausal women with obesity and type 2 diabetes mellitus who are at high risk of developing arterial stiffness and endothelial dysfunction. In this Review we discuss the relationship between obesity and hypertension with special emphasis on potential mechanisms and therapeutic targeting that might be used in a clinical setting.

Figure 1

Obesity contributes to the development of hypertension via the interaction of dietary, genetic, epigenetic and environmental factors. Visceral adipocyte dysfunction leads directly to renal, cardiac and vascular dysfunction, via an impaired immune or inflammatory response, and by affecting neuroimmune interactions that alter SNS signalling. Cardiac and/or renal abnormalities can lead to vascular dysfunction and vice-versa. Obesity-related hypertension is associated with structural and functional changes in the kidney, heart and vasculature. Hyperuricaemia might also affect adipocyte function and vascular remodelling, and cause renal abnormalities. Abbreviations: ↑, increased; ↓, decreased; Ang II, angiotensin II; DPP-4, dipeptidyl peptidase 4; MCP-1, monocyte chemoattractant protein-1; PNS, parasympathetic nervous system; RAAS, renin–angiotensin–aldosterone system; SNS, sympathetic nervous system; T_H, T helper cell; T_REG, T regulatory cell.

Figure 2

Possible mechanisms of obesity-associated hypertension and therapeutic strategies. Adipose tissue releases leptin, angiotensinogen and oxidized fatty acids to stimulate adrenal release of aldosterone via activation of the classic RAAS, as well as a non-classical pathway mediated by oxidized fatty acids. Leptin stimulates the central SNS which in turn leads to renin release from the kidney. Activation of RAAS in other tissues contributes to renal and vascular dysfunction. Increased adipose tissue can lead to OSA, which can be treated by therapeutic weight loss or application of cPAP. OSA leads to activation of the SNS which activates RAAS in the kidney. Increased aldosterone can be reduced with mineralocorticoid receptor antagonists. Abbreviations: ↑, increased; ↓, decreased; ARBs, angiotensin type 1 receptor blockers; cPAP, continuous positive airway pressure; OSA, obstructive sleep apnoea; RAAS, renin–angiotensin–aldosterone system; SNS, sympathetic nervous system.