Obesity hypertension: role of leptin and sympathetic nervous system

Abstract

Obesity may account for as much as 65% to 75% of human essential hypertension in most industrialized countries. Excess renal sodium reabsorption and a hypertensive shift of renal-pressure natriuresis play a key role in mediating obesity hypertension. Sympathetic activation contributes to obesity-induced sodium retention and hypertension because adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with other neurochemical pathways in the hypothalamus may be a partial link between excess weight gain and increased sympathetic activity. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term intravenous leptin infusions in nonobese rodents at rates that raise plasma concentrations to the levels found in severe obesity increase arterial pressure and heart rate through adrenergic activation. Also, transgenic mice that overexpress leptin develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including melanocortin-4 receptors. However, it is unclear whether this pathway or others, such as neuropeptide Y, mediate the long-term effects of leptin on blood pressure. In addition, leptin has other actions, such as stimulation of nitric oxide formation and enhancement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the precise role of these complex interactions in human obesity has not been elucidated, this is an important area for further investigation, especially considering the current epidemic of obesity in most industrialized countries.

Gender differences in ambulatory blood pressure monitoring profile in obese, overweight and normal subjects

“…Obesity is associated with hyperleptinemia: leptin, secreted by adipocytes, elicits an increase in arterial BP in obese individuals via a sympathoexcitatory central mechanism and through hyperinsulinemia. 26,27 It has also been shown that leptin induces vasorelaxation through NO-dependent as well as NO-independent mechanisms. 28 Rumantir et al 29 did not find a relationship between plasma leptin concentrations, adrenaline secretion rates, and total and regional noradrenaline spillover in lean and obese men.…”

Sympathetic Vascular Tone in Human Obesity

“…Several lines of evidence indicate that human obesity activates the sympathetic nervous system Julius et al, 2000;Hall et al, 2001]. First, sympathetic activation has been demonstrated in obesity by plasma norepinephrine measurements and 24-hour urinary norepinephrine and dopamine excretion [Troisi et al, 1991;Young et al, 1992].…”

“…Several lines of evidence indicate that obesity activates the sympathetic nervous system Julius et al, 2000;Hall et al, 2001]. Sympathoactivation has been demonstrated in human obesity by plasma norepinephrine measurements, 24-hour urinary cathecolamine excretion, measurements of radiolabeled norepinephrine spillover, microneurographic measurement of mSNA, dual α-and β-adrenergic inhibition, and systemic ganglion blockade [Troisi et al, 1991;Scherrer et al, 1994;Grassi et al, 1995;Eikelis et al, 2003;Wofford et al, 2001;Shibao et al, 2007].…”

Obésité humaine et système nerveux sympathique

“…Une telle activation sympathique aura des incidences sur le coeur, les vaisseaux et le rein (rétention sodée). L'accroissement des résistances vasculaires périphériques débouchera sur l'élévation de la pression artérielle chez l'obèse [33,35]. En revanche, inversement à ce qui est observé pour le SNS, il est à remarquer que l'activité sécrétoire de la médullo-surrénale est inchangée ou réduite chez l'obèse [29,36] ; de plus, il existe un dimorphisme sexuel notable dans les réponses induites par le jeûne ou un exercice [37].…”