Nitric Oxide and the Autonomic Nervous System

NCT00178919 | Completed Results

• 2 other identifiers: 010876NIH 1RO1HL71172
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypertension; Pure Autonomic Failure

Keywords

Endothelial Nitric Oxide; L-NMMA; Trimethaphan; Autonomic Nervous System; Nitric Oxide Inhibition

Outcome Measures

Primary Outcomes (2)

• Change in Systolic Blood Pressure

  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

  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

Study Arms (2)

Autonomic Failure Patients

EXPERIMENTAL

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; Drug: Trimethaphan

Controls and hypertensives

EXPERIMENTAL

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; Drug: Trimethaphan

Interventions

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.

Autonomic Failure Patients; Controls and hypertensives

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.

Autonomic Failure Patients; Controls and hypertensives

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult subjects.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Autonomic Dysfunction Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (2)

• Gamboa A, Shibao C, Diedrich A, Paranjape SY, Farley G, Christman B, Raj SR, Robertson D, Biaggioni I. Excessive nitric oxide function and blood pressure regulation in patients with autonomic failure. Hypertension. 2008 Jun;51(6):1531-6. doi: 10.1161/HYPERTENSIONAHA.107.105171. Epub 2008 Apr 21.

  PMID: 18426998 DERIVED

• Gamboa A, Shibao C, Diedrich A, Choi L, Pohar B, Jordan J, Paranjape S, Farley G, Biaggioni I. Contribution of endothelial nitric oxide to blood pressure in humans. Hypertension. 2007 Jan;49(1):170-7. doi: 10.1161/01.HYP.0000252425.06216.26. Epub 2006 Nov 27.

  PMID: 17130304 DERIVED

MeSH Terms

Conditions

Hypertension; Pure Autonomic Failure

Interventions

omega-N-Methylarginine; Trimethaphan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Italo Biaggioni
• Organization: Vanderbilt University

italo.biaggioni@vanderbilt.edu

615-343-6499

Study Officials

• Italo Biaggioni, M.D.

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 15, 2005
• Study Start: August 1, 2002
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: June 4, 2013
• Results First Posted: May 3, 2010

Record last verified: 2013-05

Locations

US (1)