Autonomic Nervous System and Nitric Oxide Interactions

Study Overview
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Brief Summary
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The investigators are interested in the role of the autonomic nervous system in the regulation of endothelial function among obese hypertensive subjects. In particular, the investigators will study how endothelial function (response to intra-arterial acetylcholine) changes during autonomic withdrawal.

Official Title
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The Autonomic Nervous System, Nitric Oxide and TPA Interactions

Conditions
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Endothelial Dysfunction

Intervention / Treatment
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* Drug: Trimethaphan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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For lean healthy volunteers: 20 subjects (10 males and 10 females) aged 18-60 yr. All potential volunteers will have routine blood test to screen for hepatic, renal, and hematological abnormalities. Body mass index < 25Kg/m2 . Female volunteers of childbearing potential will undergo HCG pregnancy test at screening and again on the study day. For Obese subjects with high blood pressure. 20 subjects (10 males and 10 females) aged 18-60 yr. All potential volunteers will have routine blood test to screen for hepatic, renal, and hematological abnormalities. Body mass index > 30 and less than 40 Kg/m2 *High blood pressure (systolic=130 and diastolic = 85 mmHg) Female volunteers of childbearing potential will undergo serum HCG pregnancy test at screening and urine HCG pregnancy test again on the study day. Exclusion criteria: Pregnant females Subjects unable to give voluntary informed consent Subjects on anticoagulant drugs or anemic Subjects with a recent medical illness Subjects with a history of coronary heart disease Subjects with known kidney or liver disease Subjects with recent weight loss or consuming low carbohydrate diet

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trimethaphan<br>Response to intrabrachial vasodilators during autonomic withdrawal | Drug: Trimethaphan<br>* Trimethaphan 4 mg/min IV, for the duration of the study (approximately 2 hours)<br>* Other names: Blocked;|
| Placebo Comparator: Placebo<br>Response to intrabrachial vasodilators during saline intravenous (IV) infusion | Drug: Placebo<br>* Response to intrabrachial vasodilators during IV saline infusion<br>* Other names: Intact;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Function | The dose response curve to intrabrachial vasodilators will be determined using the peak forearm blood flow during the last 5 minutes of each drug infusion | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nitric Oxide, Autonomic Nervous System