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Completed

NCT Number: NCT00178919

Nitric Oxide and the Autonomic Nervous System

The amount of blood flowing to the different parts of the body is regulated by the autonomic (automatic) nerves and by local factors produced by the blood vessels. Nitric oxide (NO) is one of the most important of these metabolic factors. If the production of NO is slowed or stopped the amount of blood to the different parts of the body is decreased. There is increasing knowledge that NO mechanisms are impaired in a number of medical conditions. NO function is reduced in patients with risk factors for atherosclerosis (hardening of the arteries) such as hypercholesterolemia (patients with high cholesterol), or diabetes mellitus, and is also impaired in smokers. This NO "deficiency" is believed to contribute to the greater cardiovascular risk that marks these patient populations. This study is designed to examine if endothelial nitric oxide is an important control mechanism of blood pressure under normal conditions, and if impairment of nitric oxide contributes to hypertension.

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Key information

Conditions

Hypertension Autonomic Nervous System Diseases Cardiovascular Diseases Nervous System Diseases Primary Dysautonomias Pure Autonomic Failure Vascular Diseases

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Autonomic Dysfunction Center

Nashville, Tennessee, 37232, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adult subjects.
  • 18 to 85 years.
  • Non-smokers or long term smokers for specific aim 6.
  • Drug-free.
  • Long term hypertension in specific substudy 3, patients with autonomic failure in specific aims 4 and 5, diabetes mellitus in specific aim 5.

Exclusion criteria

  • Being on any medication other than antihypertensives (for hypertensives), autonomic medications (for autonomic failure [AF] patients), insulin or other treatment for diabetes (for diabetic patients).
  • Having pulmonary, renal, hematopoietic, hepatic and/or cardiac disease.

Treatment and study plan

L-NMMA

Drug

IV infusion of 125, 250 and 500 mcg/Kg/min for 15 minutes each dose. The main outcome is the maximal increase in blood pressure produced at the end of the infusions or a maximal systolic blood pressure of 160 mm Hg. It could be achieved after the first dose or the third.

Trimethaphan

Drug

IV infusion for the duration of the study at 4-6 mg/min depending on autonomic blockade. This is only to produce transient pharmacological blockade of the autonomic nervous system in order to allow the full expression of the inhibition of nitric oxide synthase. There is no direct outcome associated with this intervention.

Primary outcomes

  1. Change in Systolic Blood Pressure

    Time frame: At the end of the highest tolerated dose of IV infusion of L-NMMA

    L-NMMA (nitric oxide synthase inhibitor) was infused intravenously at different doses for 15 minutes each, after blocking the autonomic nervous system with trimethaphan. The change in systolic blood pressure at the end of the highest tolerated dose is the main outcome. Trimethaphan infused intravenously was used to produce transient blockade of the autonomic nervous system to allow for a full response to nitric oxide inhibition (in the absence of the baroreflex.

  2. Systolic Blood Pressure in Response to Systemic Nitric Oxide Inhibition

    Time frame: End of 15 minutes of infusion of L-NMMA at the highest tolerated dose

    Systolic blood pressure at the highest tolerated dose of IV infusion of L-NMMA during autonomic nervous system blockade with trimethaphan. Trimethaphan, infused intravenously was used to produce transient blockade of the autonomic nervous system to allow for a full response to nitric oxide inhibition (in the absence of the baroreflex.

Sponsors and collaborators

Lead sponsor

Vanderbilt University

Other

Registry information

Official study title

Cardiovascular Regulation: Autonomic/Metabolic Mechanisms PO1 HL56693, Project 4: Cardiovascular Regulation: Autonomic/Metabolic Mechanisms

Important dates

Study start
2002
Primary completion
2008
Study completion
2008
First posted
Sep 15, 2005
Registry last updated
Jun 4, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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