Nitric Oxide and the Autonomic Nervous System

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00178919
• Other study ID #: 010876
• Secondary ID: NIH 1RO1HL71172
• Status: Completed
• Phase: N/A
• First received: September 12, 2005
• Last updated: May 24, 2013
• Start date: August 2002
• Est. completion date: August 2008

Study information

• Verified date: May 2013
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor)

Related Conditions & MeSH terms

• Hypertension
• Pure Autonomic Failure

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Autonomic Dysfunction Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No