Clinical trial NCT00178919: Nitric Oxide and the Autonomic Nervous System
Official title: Cardiovascular Regulation: Autonomic/Metabolic Mechanisms PO1 HL56693, Project 4: Cardiovascular Regulation: Autonomic/Metabolic Mechanisms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Pure Autonomic Failure
Keywords: Endothelial Nitric Oxide
L-NMMA
Trimethaphan
Autonomic Nervous System
Nitric Oxide Inhibition
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
First posted: 2005-09-15
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Systolic Blood Pressure
timeFrame: At the end of the highest tolerated dose of IV infusion of L-NMMA
measure: Systolic Blood Pressure in Response to Systemic Nitric Oxide Inhibition
timeFrame: End of 15 minutes of infusion of L-NMMA at the highest tolerated dose
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Autonomic Dysfunction Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Italo Biaggioni, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.