Role of Mitochondria-derived Oxidative Stress on Microvascular Endothelial Function in Healthy Non-Hispanic Black and White Adults
概览
- 阶段
- 2 期
- 干预措施
- Placebo
- 疾病 / 适应症
- Healthy
- 发起方
- University of Georgia
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Cutaneous microvascular responses to local heating
- 状态
- 招募中
- 最后更新
- 去年
概览
简要总结
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.
研究者
S. Tony Wolf
Assistant Professor
University of Georgia
入排标准
入选标准
- •Self-identify as either non-Hispanic Black or non-Hispanic White.
- •Men and women 18-75 years old.
- •Non-hypertensive (systolic blood pressure \[SBP\]\<130 and diastolic blood pressure \[DBP\] \<85 mmHg).
- •Have low density lipoprotein cholesterol \<150mg/dl.
- •Have HbA1C \<6.0%.
排除标准
- •Rash, skin disease, or disorders of pigmentation (e.g., psoriasis, eczema, vitiligo, or other skin inflammatory skin disorders)
- •Known skin allergies to latex or adhesives
- •Smoking and/or use of nicotine-containing products within the past year
- •Use of illegal/recreational drugs
- •Generalized kidney disease
- •Taking chloramphenicol, cholestyramine, medication for seizures, methotrexate, nitrofurantoin, tetracycline, barbiturates, steroids, phenobarbital/phenytoin, orlistat or pyrimethamine
- •Any current medications which could conceivably alter the cardiovascular control or responses
- •Diagnosed or suspected metabolic or cardiovascular disease
- •Current pregnancy or breastfeeding
- •History of skin or other cancers
研究组 & 干预措施
Placebo, then MitoQ
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
干预措施: Placebo
MitoQ, then Placebo
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
干预措施: MitoQ
MitoQ, then Placebo
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
干预措施: Placebo
MitoQ, then Placebo
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
干预措施: MitoTempo
MitoQ, then Placebo
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
干预措施: Tempol
MitoQ, then Placebo
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
干预措施: L-NAME
MitoQ, then Placebo
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
干预措施: SNP - Sodium Nitroprusside
Placebo, then MitoQ
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
干预措施: MitoQ
Placebo, then MitoQ
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
干预措施: MitoTempo
Placebo, then MitoQ
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
干预措施: Tempol
Placebo, then MitoQ
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
干预措施: L-NAME
Placebo, then MitoQ
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
干预措施: SNP - Sodium Nitroprusside
结局指标
主要结局
Cutaneous microvascular responses to local heating
时间窗: 1 hour post intervention
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.
Mitochondrial ROS production in peripheral blood mononuclear cells (PBMCs)
时间窗: 1 hour post intervention
Blood will be drawn for isolation of PBMCs and measurement of mitochondrial function and oxidative stress production.
Flow-mediated dilation responses
时间窗: 1 hour post intervention
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.