Transduction of Sympathetic Neural Activity in Human Obesity Without Hypertension

Description

In addition to chronically elevated MSNA, there is a growing recognition that hypertension in states of insulin resistance and obesity may also be attributed to an increased vascular sensitivity to MSNA (1, 2, 13, 36-38). To study this phenomenon, we quantify vascular sensitivity to MSNA using an innovative, moment-to-moment assessment of the blood pressure response following individual bursts of muscle sympathetic nerve activity (MSNA), (10, 11, 34, 37). This approach is termed 'sympathetic-vascular transduction (SVT).' We will examine the hypothesis that SVT is exaggerated in obesity and insulin resistance and is attenuated by suppression of oxidative stress. Oxidative stress is the overabundance of reactive oxygen species and is another hallmark of hypertension, obesity, and insulin resistance. Oxidative stress can be safely reduced via intravenous infusion of ascorbic acid (Vit C) (4, 28). Therefore, we will use a randomized, double-blinded, placebo-controlled approach to test the hypothesis that elevated SVT will be attenuated by suppression of oxidative stress via ascorbic acid I.V. infusion compared with saline I.V. infusion (placebo) in obese adults with insulin resistance. Our study will identify a unique mechanism that can be targeted to reduce the excessively high prevalence of hypertension and risk for CVD in obesity and insulin resistance.

Conditions

Obesity

Study Overview

Study Details

Study overview

In addition to chronically elevated MSNA, there is a growing recognition that hypertension in states of insulin resistance and obesity may also be attributed to an increased vascular sensitivity to MSNA (1, 2, 13, 36-38). To study this phenomenon, we quantify vascular sensitivity to MSNA using an innovative, moment-to-moment assessment of the blood pressure response following individual bursts of muscle sympathetic nerve activity (MSNA), (10, 11, 34, 37). This approach is termed 'sympathetic-vascular transduction (SVT).' We will examine the hypothesis that SVT is exaggerated in obesity and insulin resistance and is attenuated by suppression of oxidative stress. Oxidative stress is the overabundance of reactive oxygen species and is another hallmark of hypertension, obesity, and insulin resistance. Oxidative stress can be safely reduced via intravenous infusion of ascorbic acid (Vit C) (4, 28). Therefore, we will use a randomized, double-blinded, placebo-controlled approach to test the hypothesis that elevated SVT will be attenuated by suppression of oxidative stress via ascorbic acid I.V. infusion compared with saline I.V. infusion (placebo) in obese adults with insulin resistance. Our study will identify a unique mechanism that can be targeted to reduce the excessively high prevalence of hypertension and risk for CVD in obesity and insulin resistance.

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

Transduction of Sympathetic Neural Activity in Human Obesity Without Hypertension

Condition
Obesity
Intervention / Treatment

-

Contacts and Locations

Kansas City

University of Kansas Medical Center, Kansas City, Kansas, United States, 66160

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • 1. Obese: BMI \>25 m/kg2
  • 2. Elevated insulin resistance: HOMA-IR \> 2.5 (calculation based on fasting glucose and insulin concentrations in blood)
  • 3. Middle-aged: 35-65 years
  • 4. Participants must be willing and able to discontinue taking any vitamin C or E supplements or omega-3 fatty acids beginning 2 weeks prior.
  • 5. Able and willing to provide written informed consent
  • 1. Currently taking a statin or antihypertension medication
  • 2. Hyperlipidemia: Fasting triglycerides \< 250 mg/dL
  • 3. Hypertension: \>130/80 mmHg
  • 4. History of heart disease (e.g., myocardial infarction, stent)
  • 5. History of vascular disease (e.g., bypass, stroke)
  • 6. Individuals with narrow angle glaucoma

Ages Eligible for Study

18 Years to 79 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

University of Kansas Medical Center,

Study Record Dates

2027-09-01