Sympathetic Transduction in Obesity

Hypertension

Central (abdominal) obesity is associated with elevated adrenergic activity and arterial blood pressure (BP). Therefore, we tested the hypothesis that transduction of spontaneous muscle sympathetic nerve activity (MSNA) to BP, i.e., sympathetic transduction, is augmented in abdominal obesity (increased waist circumference) and positively related to prevailing BP.

The prevalence of obesity has increased to over 42% of adults in the United States. Obesity, particularly elevations in central adiposity, is associated with the development of hypertension, which is a prominent cause of cardiovascular diseases (CVD), such as stroke, myocardial infarction, heart failure, and chronic kidney disease. Pathophysiology of obesity hypertension includes several different categories of mechanisms, such as sympathetic activation, inflammation, and renal dysfunction. However, the relative importance and contribution of these mechanisms to the initiation of obesity hypertension remains uncertain. Obesity is characterized by elevated peripheral vascular tone. Specifically, larger decreases in arterial blood pressure (BP) were observed following ganglionic blockade (trimethaphan) in obese individuals compared with non-obese controls, suggesting greater autonomic support of BP in obesity. Similarly, 4 weeks of combined α- and β-adrenergic receptor blockade produced larger reductions in BP in obese participants with hypertension compared with non-obese control with hypertension. These data are consistent with the large body of evidence suggesting that obesity elevates muscle sympathetic nerve activity (MSNA). However, MSNA may not be elevated in obesity if development of hypertension is absent. Therefore, the extent to which MSNA contributes to the initial development of BP dysregulation in obese men and women without hypertension remains unclear. Obesity-related increases in vascular tone may be, in part, a result of increased vascular responsiveness to MSNA. In fact, elevated vascular responsiveness to MSNA has been reported in obesity-related conditions such as type 2 diabetes. However, only one study has directly examined sympathetic vascular tone in obese subjects without hypertension, reporting similar passive increases in forearm blood flow following α-adrenergic receptor blockade when compared to age- and sex-matched non-obese participants. These data suggest that obesity alone does not alter passive dilation of the forearm resulting from α-adrenergic receptor blockade. However, an extrapolation to systemic BP regulation in obesity from an examination of forearm dilation is challenging for several reasons. First, passive dilation following α-adrenergic receptor blockade may not reflect the blood flow response to α-adrenergic receptor activation, i.e., endogenous sympathetic activation. Second, in normal adults, vascular responsiveness to sympathetic innervation is heterogenous across vascular regions. For example, the lower limbs exhibit greater vascular sensitivity to sympathetic stimulation compared with the forearm vasculature as a result of greater α-adrenergic receptor density and/or sensitivity in the lower limbs. Third, obese individuals exhibit regional differences in endogenous norepinephrine kinetics compared with non-obese individuals. Thus, although regional sympathetic vascular tone has been assessed in obesity, there are limited data available regarding potential alterations in systemic BP responsiveness to endogenous activation of adrenergic receptors in this population who are highly prone to development of hypertension. Therefore, a technique that quantifies the systemic pressor response to spontaneous bursts of MSNA with high temporal resolution (i.e., sympathetic transduction) is used. It is hypothesized that sympathetic transduction would be augmented in young/middle-aged men and women with abdominal obesity (increased waist circumference) compared with age- and sex-matched non-obese controls. It is further hypothesized that augmented sympathetic transduction in obesity would be positively related to higher prevailing BP.

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