Effects of Nitrite on Blood Vessel Dilation in Normal Volunteers

NCT00048477 | Completed Phase 2

• 2 other identifiers: 03002003-H-0020
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Nitric oxide gas is important in regulating blood vessel dilation, and consequently, blood flow. This gas is continuously produced by endothelial cells, which line the blood vessels. This study will examine whether nitrite, a molecule that normally circulates in the blood stream, can also dilate blood vessels. The results of this study may be valuable in developing treatments for people with conditions associated with impaired endothelial production of nitric oxide, including high blood pressure, high blood cholesterol, diabetes, estrogen deficiency, and others. Healthy, non-smoking normal volunteers 21 years of age or older may be eligible for this study. People who lack the enzyme G6PD or cytochrome B5 in their red blood cells may not participate. Absence of these enzymes can lead to episodes of sudden shortness of breath and cyanosis (blueness of the skin due to lack of sufficient oxygen). Participants will undergo the procedures described in study Parts A and B, as follows:

• Part A - After numbing the skin, small tubes are placed in the artery and vein at the inside of the elbow of the dominant arm (right- or left-handed) and a small tube is placed in a vein of the other arm. The tubes are used for infusing saline (salt water) and for drawing blood samples. A pressure cuff is placed around the upper part of the dominant arm, and a rubber band device called a strain gauge is also placed around the arm to measure blood flow. When the cuff is inflated, blood flows into the arm, stretching the strain gauge at a rate proportional to the flow. Grip-strength of the dominant arm is measured with a dynamometer to determine maximum grip-strength. Then, several measurements of blood flow, nitrite, hemoglobin, and handgrip are made before and after administration of L-NMMA, a drug that blocks endothelial production of nitric oxide.
• Part B - Part A testing is repeated, except that sodium nitrite dissolved in a saline solution is infused into the artery of the forearm for a few minutes before and during the hand-grip exercises. In addition, blood samples are drawn before and after each handgrip exercise to measure methemoglobin, a substance that, at excessive levels, can cause adverse side effects.

Conditions

Nitric Oxide; Endothelium-Derived Relaxing Factor; Healthy

Keywords

Endothelium; Vasodilation; Exercise; Hemoglobin; Blood Flow; Healthy Volunteer; HV

Interventions

L-NMMA and Sodium Nitrite DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All volunteer subjects must be at least 21 years of age in good health and have provided informed, written consent for participation in this study.

You may not qualify if:

• Subjects with a history or evidence of present or past hypertension (blood pressure greater than 145/95 mmHg), hypercholesterolemia (LDL cholesterol greater than 130 mg/dL), diabetes mellitus (fasting blood glucose greater than 130 mg/dL), smoking within two years, cardiovascular disease, peripheral vascular disease, coagulopathy, or any other disease predisposing to vasculitis or Raynaud's phenomenon.
• Subjects with a known cytochrome B5 deficiency will not participate in this study.
• Subjects with a history of reaction to a medication or other substance characterized by dyspnea and cyanosis will not participate in this study.
• Subjects with a baseline methemoglobin level greater than 1% will not receive nitrite infusions.
• Lactating and pregnant females.
• No volunteer subject will be allowed to take any medication (oral contraceptive agents are allowed), vitamin supplements, herbal preparations, nutriceuticals or other 'alternative therapies' for at least one month prior to study and will not be allowed to take aspirin for one week prior to study.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Heart, Lung and Blood Institute (NHLBI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373-6. doi: 10.1038/288373a0.

  PMID: 6253831 BACKGROUND

• Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11-17;327(6122):524-6. doi: 10.1038/327524a0.

  PMID: 3495737 BACKGROUND

• Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664-6. doi: 10.1038/333664a0.

  PMID: 3131684 BACKGROUND

MeSH Terms

Conditions

Aneurysm; Motor Activity

Interventions

omega-N-Methylarginine; Sodium Nitrite

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Behavior

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Nitrites; Nitrous Acid; Nitrogen Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 31, 2002
• First Posted: November 1, 2002
• Study Start: October 1, 2002
• Study Completion: November 1, 2003
• Last Updated: March 4, 2008

Record last verified: 2003-11

Locations

US (1)