The Influence of Mitochondrial-Derived Reactive Oxygen Species on Racial Disparities in Neurovascular Function

The Influence of Mitochondrial-Derived Reactive Oxygen Species on Racial Disparities in Neurovascular Function

Black individuals are at increased cardiovascular disease risk. The central goal of the study is to determine if mitochondrial reactive oxygen species influence blood vessel function and nervous system regulation of blood pressure differentially in black, compared to white individuals. These findings may help to explain a potential mechanism that contributes to racial disparities in blood pressure and cardiovascular disease risk. A secondary goal is to determine if mitochondrial reactive oxygen species improves blood pressure and vascular function in individuals with elevated blood pressure and stage 1 hypertension.

The prevalence of hypertension in black adults is higher than in any other race/ethnicity in the US, and among the highest in the world. Hypertension is a risk factor for several major cardiovascular diseases. Racial disparities in blood vessel function are well documented. Moreover, racial disparities in hypertension persist despite advances in pharmacotherapies. Therefore, a major knowledge gap remains in identifying the mechanism(s) underlying racial disparities in hypertension, and ultimately cardiovascular diseases.

Our goal is to investigate reasons for the higher prevalence of blood vessel dysfunction and hypertension in black individuals, and to identify effective preventive strategies. Excess free radicals contribute to blood vessel dysfunction, kidney dysfunction, and thus hypertension as both blood vessel health and the kidneys contribute to blood pressure regulation. Moreover, excess free radicals contribute to blood vessel dysfunction in black adults. Mitochondria are a major source of free radicals. Mitochondria antioxidants improve blood vessel function in rodents and in human trials. A prior aging study demonstrated that acute MitoQ (single 160mg-dose mitoquinone) restored blood vessel function in older adults. Anohter recent study demonstrated that a single 80mg dose elicited similar improvements in adults with peripheral artery disease. however, the role of mitochondrial free radicals in racial disparites in blood vessel function is unclear. Our central hypothesis is that mitochondrial free radicals play a role in reduced blood vessel function and kidney in black adults. We will test our hypothesis using a randomized, placebo-controlled, crossover design, acute MitoQ supplement study in black and white adults (we will not exclude other races though). We will also measure blood pressure and urine biomarkers that are indicative of kidney injury in this proposal.

Regarding methodology, we will perform blood draws, vascular testing, and record nervous system activity before and one hour after acute MitoQ and placebo consumption. We will also measure urine biomarkers of kidney function and blood pressure in the hours following acute MitoQ and placebo consumption in adults (19-75 years old).

Inclusion Criteria:

• Are between the ages of 19-75.
• Have blood pressure no higher than 150/90 mmHg.
• Have a BMI below 35 Kg/m2 (otherwise healthy)
• Free from metabolic disease (diabetes or renal disease), pulmonary disorders (e.g., COPD & cystic fibrosis), and cardiovascular disease (peripheral vascular, cardiac, or cerebrovascular).
• Do not have any precluding medical issues that prevent participants from exercising (i.e., cardiovascular issues, or muscle/joint issues including painful arthritis) or giving blood (e.g., blood thinners).
• Are not currently smoking, using smokeless tobacco, nor smoked within the past 12 months.

Exclusion Criteria:

• Known allergy to MitoQ
• High blood pressure - greater the 150/90 mmHg
• Low blood pressure - less than 90/50 mmHg
• History of cardiovascular disease
• History of cancer
• History of diabetes
• History of kidney disease
• Obesity (BMI > 30 kg/m2)
• Smoking or tobacco use
• Current pregnancy
• Nursing mothers
• Communication barriers