Neural Mechanism of Aldosterone-induced Insulin Resistance
| Status: | Recruiting |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Endocrine |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 3/27/2019 |
| Start Date: | November 2010 |
| End Date: | December 2020 |
| Contact: | Debbie Arbique, DNP |
| Email: | debbie.arbique@utsouthwestern.edu |
| Phone: | (214)648-3188 |
The Role of Aldosterone on Sympathetic Nerve Activity and Insulin Sensitivity
Patients with high aldosterone hormone have higher blood glucose than normal people. This
study is being done to understand how aldosterone hormone affects the nerve activity that
controls blood flow in the muscles and blood glucose. The information may be helpful in
selecting blood pressure medications which can improve not only blood pressure but also
improve blood sugar.
study is being done to understand how aldosterone hormone affects the nerve activity that
controls blood flow in the muscles and blood glucose. The information may be helpful in
selecting blood pressure medications which can improve not only blood pressure but also
improve blood sugar.
Patients with primary aldosteronism are known to have impaired insulin sensitivity, which is
improved after removal of aldosterone-producing adenoma. In patients with essential
hypertension, plasma aldosterone levels have been also shown to positively correlate with
indices of insulin resistance.
Mechanism underlying aldosterone-induced insulin resistance is unknown. Aldosterone has been
shown to interfere with insulin signaling the vascular cells by increasing production of
reactive oxygen species via activation of NADPH oxidase, resulting in decreased availability
of nitric oxide (NO), the key mediator for insulin-mediated vasodilation. Treatment with
mineralocorticoid receptor antagonists has been shown to improve insulin sensitivity in mice
with obesity and metabolic syndrome. Aldosterone has also been shown to increase resting
sympathetic vasoconstrictor activity to the peripheral circulation. However, effects of
aldosterone and mineralocorticoid receptor antagonists on insulin-mediated skeletal muscle
vasodilation, sympathetic activation, and vascular oxidative stress have not been assessed in
humans.
The investigators will collect venous endothelial cells, and measure skeletal muscle
microvascular perfusion using Octafluoropropane microbubble contrast agents, and measure
sympathetic nerve activity in normotensive controls (NT), stage 1 essential hypertensive
subjects (ET), and patients with primary aldosteronism (PA) during hyperinsulinemic
euglycemic clamp.
improved after removal of aldosterone-producing adenoma. In patients with essential
hypertension, plasma aldosterone levels have been also shown to positively correlate with
indices of insulin resistance.
Mechanism underlying aldosterone-induced insulin resistance is unknown. Aldosterone has been
shown to interfere with insulin signaling the vascular cells by increasing production of
reactive oxygen species via activation of NADPH oxidase, resulting in decreased availability
of nitric oxide (NO), the key mediator for insulin-mediated vasodilation. Treatment with
mineralocorticoid receptor antagonists has been shown to improve insulin sensitivity in mice
with obesity and metabolic syndrome. Aldosterone has also been shown to increase resting
sympathetic vasoconstrictor activity to the peripheral circulation. However, effects of
aldosterone and mineralocorticoid receptor antagonists on insulin-mediated skeletal muscle
vasodilation, sympathetic activation, and vascular oxidative stress have not been assessed in
humans.
The investigators will collect venous endothelial cells, and measure skeletal muscle
microvascular perfusion using Octafluoropropane microbubble contrast agents, and measure
sympathetic nerve activity in normotensive controls (NT), stage 1 essential hypertensive
subjects (ET), and patients with primary aldosteronism (PA) during hyperinsulinemic
euglycemic clamp.
Inclusion Criteria:
1. Normotensive controls
2. Stage I (140-159/90-99 mmHg) untreated subjects with essential hypertension
3. Patients with PA and stage I (140-159/90-99 mmHg) hypertension
Exclusion Criteria:
1. Congestive heart failure or coronary artery disease
2. Blood pressure averaging > 159/99 mmHg
3. Serum creatinine > 1.5 mg/dL
4. Diabetes mellitus or other systemic illness
5. Left ventricular hypertrophy by echocardiography or ECG
6. Pregnancy
7. Hypersensitivity to spironolactone, chlorthalidone, amlodipine, human recombinant
insulin or Definity
8. Any history of substance abuse (other than tobacco)
9. History of gouty arthritis
10. Patients with right-to-left, bi-directional, or transient right-to-left cardiac shunts
11. Hypersensitivity to perflutren, blood, blood products or albumin
We found this trial at
1
site
2201 Inwood Rd
Dallas, Texas 75235
Dallas, Texas 75235
(214) 645-8300
Phone: 214-648-3188
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