Abstract P188: Mitochondrial Redox Phenotype Contributes to Angiotensin Induced Hypertension
Oxidant stress contributes to the initiation and progression of hypertension by contributing to endothelial dysfunction and/or causing perturbations in nitric oxide homeostasis. Differences in mitochondrial function may contribute to this process and provide insight into why age of onset and clinical outcomes differ amongst individuals form distinct ethnic groups. We have previously demonstrated that variations in normal mitochondrial function and oxidant production exist in endothelial cells from individuals of Caucasian and African American ethnicity and that this variation contributes to endothelial dysfunction. To model these distinct mitochondrial redox phenotypes we used the C57Bl/6J (6J) and C57Bl/6NJ (NJ) that also display unique mitochondrial redox phenotypes due to the differential expression nicotinamide nucleotide transhydrogenase. Interestingly, we found that the 6J animals had a significantly higher systolic blood pressure compared to the NJ animals (116 ± 0.96 vs 102 ± 2.39 mmHg) that was exacerbated by angiotensin II induced hypertension (159 ± 8.25 vs 136 ± 4.33 mmHg). Vascular oxidative stress was assessed in these animals by evaluating mitochondrial oxygen utilization and oxidant production in primary aortic endothelial cells (MAEC) from these animals. Bioenergetic analysis indicates that compared to NJ, 6J MAEC utilized significantly less oxygen for ATP production, possess a lower maximal respiratory capacity (17.31 ± 1.84 vs 41.87 ± 2.95 pmol O2/min/ug protein), and have reduced electron leak. 6J MAEC also produce more superoxide compared to NJ in response to angiotensin II stimulation (0.08 ± 0.004 vs 0.11 ± 0.006 nmol/mg protein). Additionally, isolated renal mitochondria and vessel myography indicated differences in respiratory coupling ratios and endothelial dependent vasodilation amongst the groups. Taken together, these data indicate that differences in “normal” mitochondrial function amongst ethnic groups could contribute to a unique mitochondrial redox phenotype that influences individual susceptibility by contributing to endothelial dysfunction, providing important insights into the mechanisms that contribute to the development of hypertension.
Author Disclosures: A. Neville: None. I. Leskov: None. D. Krzywanski: None.
- © 2015 by American Heart Association, Inc.