Nitric Oxide and the Autonomic Nervous System

May 24, 2013 updated by: Italo Biaggioni, Vanderbilt University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

112

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Autonomic Dysfunction Center

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.

Eligibility Criteria

Ages Eligible for Study

16 years to 83 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Autonomic Failure Patients
To compare the effects of NO inhibition during intact and transient pharmacological blockade of the autonomic nervous system in Patients with Autonomic Failure.
Drug: L-NMMA
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.
Drug: Trimethaphan
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.
Experimental: Controls and hypertensives
To compare the effects of NO inhibition during intact and transient pharmacological blockade of the autonomic nervous system in normal volunteers and hypertensive subjects.
Drug: L-NMMA
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.
Drug: Trimethaphan
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At the end of the highest tolerated dose of IV infusion of L-NMMA
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.
End of 15 minutes of infusion of L-NMMA at the highest tolerated dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2002

Primary Completion (Actual)

August 1, 2008

Study Completion (Actual)

August 1, 2008

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 15, 2005

Study Record Updates

Last Update Posted (Estimate)

June 4, 2013

Last Update Submitted That Met QC Criteria

May 24, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 010876
  • NIH 1RO1HL71172

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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