Role of sympathetic nervous system and neuropeptides in obesity hypertension

Abstract

Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in nonobese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R). However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this remains a fruitful area for further investigation, especially in view of the current epidemic of obesity in most industrialized countries. Correspondence

Mechanisms of obesity-induced hypertension

“…As a consequence of an incomplete compensation, however, extracellular-fluid volume is expanded, resulting in a hypertensive adjustment of the pressure natriuresis. 8 This resetting of the kidney-fluid apparatus to a hypertensive level is consistent with the model of hypertension because of volume overload. Another significant cause of shift of pressure natriuresis toward higher BP levels in obesity is the possibility of alterations in intrarenal forces caused by histological changes in the renal medulla that may compress the loops of Henle and vasa recta.…”

“…7 Furthermore, pharmacological blockade of adrenergic activity in experimental models (combined a-and b-adrenergic blockade or central sympathetic modulation by clonidine) markedly blunted the rise of BP in dogs fed a high-fat diet. 8 Similar results have been reported for human beings. Combined a-and b-adrenergic blockade significantly reduced BP in obese compared with lean patients with essential hypertension.…”

“…Leptin's primary effects on the hypothalamic neuronal systems include a decrease in food consumption and upregulation of thermogenesis and energy expenditure, through stimulation of sympathetic activity. 8,48 These effects are mediated by two major pathways, one posting a positive-regulating action through expression of the propiomelanocortin-derived peptides-a melanocyte-stimulating hormone (a-MSH)-driven by high leptin levels, and the other exhibiting the opposite actions through the expression of agouti-related peptide and neuropeptide Y (NPY). a-MSH molecules bind to melanocortin 3 and 4 receptors (MC3R and MC4R), act as agonists, stimulate the SNS, increase energy expenditure and activate the hypothalamus-pituitary-adrenal axis.…”

Leptina e aldosterona na atividade simpática na hipertensão resistente, com ou sem Diabetes Tipo 2

“…The evidence that increasing plasma leptin to levels similar to those found in obesity raises arterial pressure in non-obese rats is consistent with the hypothesis that leptin is an important link between obesity, sympathetic activity and hypertension 24 . Since obesity plays a major role in contributing to human essential hypertension, it is not surprising that plasma leptin concentrations are often elevated in hypertensive patients, or that leptin and blood pressure are correlated 24 .…”

Relationship of Left Ventricular Mass with BMI and Insulin Resistance in Normotensive Obese Women

“…Obese people have higher cardiac debi with lower peripheral resistance (3). The increase in cardiac debi and blood volume activates the sympathetic nervous system and results in hypertension via several mechanisms (12,13). Increased filling pressure and volume induce left ventricular dilatation; myocardial mass then increases and gives rise to eccentric left ventricular hypertrophy.…”