The Role of Aldosterone in Obesity-Related Hypertension

Abstract

Obese subjects often have hypertension and related cardiovascular and renal diseases, and this has become a serious worldwide health problem. In obese subjects, impaired renal-pressure natriuresis causes sodium retention, leading to the development of salt-sensitive hypertension. Physical compression of the kidneys by visceral fat and activation of the sympathetic nervous system, renin-angiotensin systems (RAS), and aldosterone/mineralocorticoid receptor (MR) system are involved in this mechanism. Obese subjects often exhibit hyperaldosteronism, with increased salt sensitivity of blood pressure (BP). Adipose tissue excretes aldosterone-releasing factors, thereby stimulating aldosterone secretion independently of the systemic RAS, and aldosterone/MR activation plays a key role in the development of hypertension and organ damage in obesity. In obese subjects, both salt sensitivity of BP, enhanced by obesity-related metabolic disorders including aldosterone excess, and increased dietary sodium intake are closely related to the incidence of hypertension. Some salt sensitivity-related gene variants affect the risk of obesity, and together with salt intake, its combination is possibly associated with the development of hypertension in obese subjects. With high salt levels common in modern diets, salt restriction and weight control are undoubtedly important. However, not only MR blockade but also new diagnostic modalities and therapies targeting and modifying genes that are related to salt sensitivity, obesity, or RAS regulation are expected to prevent obesity and obesity-related hypertension.

Keywords: aldosterone; blood pressure; hypertension; obesity; salt; salt sensitivity of blood pressure..

Figure 1.

The blood pressure (BP)–natriuresis curve of obese subjects. In obese subjects, the increased glomerular filtration rate and renal blood flow induce increased renal sodium absorption, which in turn initiates impaired renal-pressure natriuresis, resulting in hypertension. Because obese hypertensive subjects require a higher BP than lean normotensive subjects to maintain the sodium balance, the BP–natriuresis curve is slanted and shifted to the right, indicating impaired renal-pressure natriuresis. As a result, obese patients exhibit salt-sensitive hypertension.

Figure 2.

The mechanism underlying obesity-related hypertension and kidney impairment. Obesity induces functional vasodilation to fulfill the increased metabolic demand of the tissue. In the early stage of obesity, the increased renal blood flow induces an increase in renal sodium reabsorption, which in turn initiates impaired renal-pressure natriuresis. Physical compression of the kidneys by increased visceral fat, hyperinsulinemia, and hyperaldosteronemia and activation of the SNS, RAS, and aldosterone/MR system also promote renal tubular sodium absorption. Prolonged hypertension, glomerular hyperfiltration, and neurohumoral activation cause further severe glomerular injury, increased impairment of renal-pressure natriuresis, and HTN and finally result in gradual nephron loss and kidney disease. Abbreviations: ARF, aldosterone-releasing factor; CKD, chronic kidney disease; CVD, cardiovascular disease; HTN, hypertension; MR, mineralocorticoid receptor; RAS, renin–angiotensin systems; SNS, sympathetic nervous system.

Figure 3.

High salt intake increases the risk of obesity. The level of salt intake proportionally increases with the incidence of hypertension and obesity. Obese subjects consume more salt and exhibit a higher salt sensitivity of BP than lean subjects, and this is synergistically enhanced by obesity-induced homeostatic environmental changes, including a large amount of visceral fat, hyperaldosteronemia, and metabolic disorders. Abbreviations: BP, blood pressure; SS, salt-sensitive.