Vascular Effects of Endothelium-Derived Versus Hemoglobin-Transported Nitric Oxide in Healthy Subjects

NCT00001963 | Completed Phase 1

• 2 other identifiers: 00003100-H-0031
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Nitric oxide (NO) is a soluble gas, continuously synthesized by the endothelium, that contributes importantly to vasodilator tone of the coronary and systemic circulations by activating guanylyl cyclase in vascular smooth muscle, causing relaxation. Although regional synthesis of NO by the endothelium contributes to local vasodilator tone, Stamler and co-workers have proposed that regional vascular tone may also be regulated by NO transported from the lungs by hemoglobin as a consequence of enhanced binding of NO to reactive thiols of oxygenated hemoglobin. This study is designed to determine the contribution of hemoglobin-transported NO to forearm microvascular dilator tone in healthy subjects at rest and during regional hypoxia associated with forearm exercise stress, with measurements made before and after regional blockade of endothelial NO synthesis. Findings in this study may be relevant to understanding the physiological contribution and therapeutic potential of hemoglobin-transported NO in the regulation of vasodilator tone in diseases and conditions associated with regional endothelial dysfunction and reduced endothelial NO bioactivity (e.g., hypertension, diabetes mellitus, hypercholesterolemia, cigarette smoking, and estrogen deficiency).

Conditions

Diabetes Mellitus; Healthy; Hypercholesterolemia; Hypertension

Keywords

Blood Flow; Exercise; Microcirculation; S-nitrosohemoglobin; Vasodilation; Healthy Volunteer

Interventions

hemoglobin-transported nitric oxide PROCEDURE

Eligibility Criteria

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

All volunteer subjects must be between 21 and 75 years of age, in good health, and must have provided informed, written consent for participation in this study. No 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 120 mg/dL), smoking within 2 years, cardiac disease, peripheral vascular disease, coagulopathy, or any other disease predisposing to vasculitis or Raynaud's phenomenon. No volunteer subject will be allowed to take any medication (oral contraceptive agents are allowed) or vitamin supplements for at least one month prior to study and will not be allowed to take aspirin for one week prior to study. Pregnancy testing will be required of all women of reproductive age to exclude current pregnancy.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

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)

• Jia L, Bonaventura C, Bonaventura J, Stamler JS. S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature. 1996 Mar 21;380(6571):221-6. doi: 10.1038/380221a0.

  PMID: 8637569 BACKGROUND

• Gow AJ, Stamler JS. Reactions between nitric oxide and haemoglobin under physiological conditions. Nature. 1998 Jan 8;391(6663):169-73. doi: 10.1038/34402.

  PMID: 9428761 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

Diabetes Mellitus; Hypercholesterolemia; Hypertension; Motor Activity; Aneurysm

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Vascular Diseases; Cardiovascular Diseases; Behavior

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 18, 2000
• First Posted: December 10, 2002
• Study Start: December 1, 1999
• Study Completion: October 1, 2000
• Last Updated: March 4, 2008

Record last verified: 1999-11

Locations

US (1)