Sympathetic Transduction in Obesity

Hypertension Clinical Trial

Official title:

Concomitantly Higher Resting Arterial Blood Pressure and Transduction of Sympathetic Neural Activity in Human Obesity Without Hypertension

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05590546
• Other study ID #: TRANSDUCTION_IN_OBESITY
• Status: Not yet recruiting
• Start date: October 19, 2022
• Est. completion date: December 19, 2022

Study information

• Verified date: October 2022
• Source: University of Kansas Medical Center
• Contact: Seth Holwerda
• Phone: 9729223230
• Email: sholwerda[@]kumc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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, to our knowledge, 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, we employed a technique that quantifies the systemic pressor response to spontaneous bursts of MSNA with high temporal resolution (i.e., sympathetic transduction). We 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. We further hypothesized that augmented sympathetic transduction in obesity would be positively related to higher prevailing BP.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 28
• Est. completion date: December 19, 2022
• Est. primary completion date: November 19, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 35 Years to 65 Years

Eligibility

Inclusion Criteria: Nonsmokers and free of metabolic or neurological disease, waist circumference > 102 cm for men and > 88 cm for women or waist circumference was < 94 cm for men and < 80 cm for women.

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Exclusion Criteria: Exclusion criteria included use of anti-hypertensive medications, history of diabetes, and history of smoking within 3 months prior to study participation, hypertension determined by 24-hour ambulatory average BP (<130/80 mmHg).

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Related Conditions & MeSH terms

• Hypertension

Intervention

Other:
• No intervention
No intervention, only performing cross-sectional analysis of pooled data collected in previous studies

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Kansas Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sympathetic transduction	signal averaging was performed in which bursts of MSNA act as a trigger and beat-to-beat BP was tracked for 15 subsequent cardiac cycles thereafter.	15 min