Dissociation Between Sympathetic Nerve Traffic and Sympathetically Mediated Vascular Tone in Normotensive Human Obesity

Abstract

Obesity increases the risk of hypertension and its cardiovascular complications. This has been partly attributed to increased sympathetic nerve activity, as assessed by microneurography and catecholamine assays. However, increased vasoconstriction in response to obesity-induced sympathoactivation has not been unequivocally demonstrated in obese subjects without hypertension. We evaluated sympathetic α-adrenergic vascular tone in the forearm by brachial arterial infusion of the α-adrenoreceptor antagonist phentolamine (120 µg/min) in normotensive obese (daytime ambulatory arterial pressure: 123 ± 1/77 ± 1 mm Hg; body mass index: 35 ± 1 kg/m2) and lean (daytime ambulatory arterial pressure: 123 ± 2/77 ± 2 mm Hg; body mass index: 22 ± 1 kg/m2) subjects (n = 25 per group) matched by blood pressure, age, and gender. Microneurographic sympathetic nerve activity to skeletal muscle was significantly higher in obese subjects (30 ± 3 versus 22 ± 1 bursts per minute; P = 0.02). Surprisingly, complete α-adrenergic receptor blockade by phentolamine (at concentrations sufficient to completely inhibit norepinephrine and phenylephrine-induced vasoconstriction) caused equivalent vasodilatation in obese (−57 ± 2%) and lean subjects (−57 ± 3%; P = 0.9). In conclusion, sympathetic vascular tone in the forearm circulation is not increased in obese normotensive subjects despite increased sympathetic outflow. Vasodilator factors or mechanisms occurring in obese normotensive subjects could oppose the vasoconstrictor actions of increased sympathoactivation. Our findings may help to explain why some obese subjects are protected from the development of hypertension.

The pathophysiology of hypertension in patients with obesity

“…In individuals who have obesity but are normotensive the observed increase in sympathetic outflow to the forearm musculature does not lead to an increase in peripheral sympathetic vascular tone. 129 The authors speculated that a dissociation between SNS activity and peripheral vascular tone can protect a subset of individuals with obesity from developing hypertension, which might explain the small population of individuals with obesity but normal blood pressure. 129 However, definitive evidence that hypertension in individuals with obesity is either initiated or maintained solely by a neurogenic mechanism has yet to be determined.…”

Should the sympathetic nervous system be a target to improve cardiometabolic risk in obesity?

“…One longitudinal study has shown that even a modest weight gain of 5 kg was associated with increased MSNA in young men who were not obese (45). Whether augmented sympathetic activity to the skeletal muscle bed translates into elevated sympathetic vasoconstrictor activity is at present unclear because complete ␣-adrenergic receptor blockade by phentolamine was found to cause equivalent vasodilatation in subjects with obesity and lean normotension (1). However, animal studies recently documented that sympathetic nerve-mediated vasoconstriction is augmented in rat mesenteric resistance arteries during dietinduced obesity.…”

Obesity-induced increases in sympathetic nerve activity: Sex matters

“…In both humans and animals, it appears that obesity (before development of metabolic syndrome) simultaneously impairs sympathetically- or alpha-adrenergic-mediated vasoconstriction (Belin de Chantemele et al, 2011;Jerez et al, 2012;Romanko & Stepp, 2005;Agapitov et al, 2008), which tends to minimize increases in AP. However, increased α-adrenergic sensitivity has been reported in humans once insulin resistance sufficient to increase plasma glucose concentration ensues (Sivitz et al, 2007).…”