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Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, and the non-Hispanic Black (NHB) population is disproportionately affected. Our research has previously demonstrated that oxidative stress may contribute to reduced vascular function in otherwise healthy NHB adults, potentially predisposing them to the development of hypertension and CVD. This study is designed to examine whether the mitochondria are an important source of oxidative stress-induced vascular dysfunction in healthy NHB adults.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MitoQ, then Placebo | Experimental | Participants will be given a single dose of 80mg MitoQ supplement first following an overnight fast. Then they will receive a matched Placebo single dose within a minimum 14 days |
|
| Placebo, then MitoQ | Experimental | Participants will be given a single dose of Placebo (matched to 80mg MitoQ) first following an overnight fast. Then they will receive 80mg MitoQ supplement single dose within a minimum of 14 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MitoQ | Dietary Supplement | MitoQ supplement is composed of mitoquinol mesylate, which is a synthetic analog of coenzyme Q10 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cutaneous microvascular responses to local heating | Using intradermal microdialysis, skin blood vessels will be locally treated with a mitochondria-targeted antioxidant (MitoTempo; 1 mM concentration). Nitric oxide (NO)-mediated skin vasodilation will be quantified via local inhibition of endothelial NO synthase during the course of the local skin heating protocol using L-NAME (15 mM concentration). Finally, maximal skin blood flow will be measured by heating the local area of skin to 43 degrees Celsius and locally perfusing sodium nitroprusside (SNP; an NO donor; 28 mM concentration). Two (2) thin fiber optic laser Doppler flowmeter probes and their holders, containing local heaters, will be used to measure skin blood flow. | 1 hour post intervention |
| Flow-mediated dilation responses | FMD measures the health of blood vessels. The ultrasound makes sound waves to measure the size of blood vessels and the speed of the blood during rest and occlusion. The cuff is inflated to 220 mmHg (a commonly-used suprasystolic pressure; i.e., arterial blood flow is completely occluded) for 5 minutes to stop blood flow to and from the forearm. | 1 hour post intervention |
| Mitochondrial ROS production in peripheral blood mononuclear cells (PBMCs) | Blood will be drawn for isolation of PBMCs and measurement of mitochondrial function and oxidative stress production. | 1 hour post intervention |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| S. Tony Wolf | Contact | 706-542-4378 | stwolf@uga.edu | |
| Melissa Gorejena | Contact | mgorejena@uga.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ramsey Student Center, University of Georgia | Recruiting | Athens | Georgia | 30602 | United States |
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C429014 | mitoquinone |
| C555916 | MitoTEMPO |
| C001803 | tempol |
| D019331 | NG-Nitroarginine Methyl Ester |
| ID | Term |
|---|---|
| D001120 | Arginine |
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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For the experimental visits, participants will receive an antioxidant supplement in capsule form or a matching placebo pill in a randomized, double-blinded, crossover fashion. During each visit, participants will be given a single dose of the treatment to which they are randomized upon arrival at the laboratory (i.e., either 80 mg MitoQ or placebo will be administered on Visit 3, and the other treatment will be given on Visit 4). Peak concentrations of the antioxidant (MitoQ) occur after approximately 1 hour, allowing for appropriate time to prepare the participant for the experimental procedures.
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| Placebo | Dietary Supplement | MitoQ matched Placebo |
|
| MitoTempo | Drug | During each experimental visit, intradermal microdialysis will be used to locally infuse MitoTempo (a mitochondria-specific superoxide dismutase mimetic) into the cutaneous microvasculature in the ventral aspect of the left forearm. |
|
| Tempol | Drug | During each experimental visit, intradermal microdialysis will be used to locally infuse Tempol (a superoxide dismutase mimetic) into the cutaneous microvasculature in the ventral aspect of the left forearm. |
|
| L-NAME | Drug | During each experimental visit, L-NAME (nitric oxide synthase inhibitor) will be perfused through microdialysis fibers for quantification of nitric oxide-mediated vasodilation. |
|
| SNP - Sodium Nitroprusside | Drug | At the end of each experimental visit, SNP will be perfused through microdialysis fibers to elicit a maximal vasodilation response. |
|
| D000599 |
| Amino Acids, Diamino |