Browsing by Author "Kirkman, Danielle L."
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Effects of a mitochondrial-targeted ubiquinol on vascular function and exercise capacity in chronic kidney disease: a randomized controlled pilot study(American Journal of Physiology - Renal Physiology, 2023-10-01) Kirkman, Danielle L.; Stock, ,Joseph M.; Shenouda, Ninette; Bohmke, Natalie J.; Kim, Youngdeok; Kidd, Jason; Townsend, Raymond R.; Edwards, David G.Mitochondria-derived oxidative stress has been implicated in vascular and skeletal muscle abnormalities in chronic kidney disease (CKD). The purpose of this study was to investigate the effects of a mitochondria-targeted ubiquinol (MitoQ) on vascular function and exercise capacity in CKD. In this randomized controlled trial, 18 patients with CKD (means ± SE, age: 62 ± 3 yr and estimated glomerular filtration rate: 45 ± 3 mL/min/1.73 m2) received 4 wk of 20 mg/day MitoQ (MTQ group) or placebo (PLB). Outcomes assessed at baseline and follow-up included macrovascular function measured by flow-mediated dilation, microvascular function assessed by laser-Doppler flowmetry combined with intradermal microdialysis, aortic hemodynamics assessed by oscillometry, and exercise capacity assessed by cardiopulmonary exercise testing. Compared with PLB, MitoQ improved flow-mediated dilation (baseline vs. follow-up: MTQ, 2.4 ± 0.3% vs. 4.0 ± 0.9%, and PLB, 4.2 ± 1.0% vs. 2.5 ± 1.0%, P = 0.04). MitoQ improved microvascular function (change in cutaneous vascular conductance: MTQ 4.50 ± 2.57% vs. PLB −2.22 ± 2.67%, P = 0.053). Central aortic systolic and pulse pressures were unchanged; however, MitoQ prevented increases in augmentation pressures that were observed in the PLB group (P = 0.026). MitoQ did not affect exercise capacity. In conclusion, this study demonstrates the potential for a MitoQ to improve vascular function in CKD. The findings hold promise for future investigations of mitochondria-targeted therapies in CKD. NEW & NOTEWORTHY In this randomized controlled pilot study, we investigated the effects of a mitochondria-targeted ubiquinol (MitoQ) on vascular function and exercise capacity in chronic kidney disease. Our novel findings showed that 4-wk supplementation of MitoQ was well tolerated and improved macrovascular endothelial function, arterial hemodynamics, and microvascular function in patients with stage 3–4 chronic kidney disease. Our mechanistic findings also suggest that MitoQ improved microvascular function in part by reducing the NADPH oxidase contribution to vascular dysfunction.Item Melatonin supplementation does not alter vascular function or oxidative stress in healthy normotensive adults on a high sodium diet(Physiological Reports, 2023-12-18) Ramos Gonzalez, Macarena; Axler, Michael R.; Kaseman, Kathryn E.; Lobene, Andrea J.; Farquhar, William B.; Witman, Melissa A.; Kirkman, Danielle L.; Lennon, Shannon L.High sodium diets (HSD) can cause vascular dysfunction, in part due to increases in reactive oxygen species (ROS). Melatonin reduces ROS in healthy and clinical populations and may improve vascular function. The purpose was to determine the effect of melatonin supplementation on vascular function and ROS during 10 days of a HSD. We hypothesized that melatonin supplementation during a HSD would improve vascular function and decrease ROS levels compared to HSD alone. Twenty-seven participants (13 M/14 W, 26.7 ± 2.9 years, BMI: 23.6 ± 2.0 kg/m2, BP: 110 ± 9/67 ± 7 mmHg) were randomized to a 10-day HSD (6900 mg sodium/d) supplemented with either 10 mg of melatonin (HSD + MEL) or a placebo (HSD + PL) daily. Brachial artery flow-mediated dilation, a measure of macrovascular function, (HSD + PL: 7.1 ± 3.8%; HSD + MEL: 6.7 ± 3.4%; p = 0.59) and tissue oxygenation index (TSI) reperfusion rate, a measure of microvascular reactivity, (HSD + PL: 0.21 ± 0.06%/s; HSD + MEL: 0.21 ± 0.08%/s; p = 0.97) and TSI area under the curve (HSD + PL: 199899 ± 10,863 a.u.; HSD + MEL: 20315 ± 11,348 a.u.; p = 0.17) were similar at the end of each condition. Neither nitroxide molarity (HSD + PL: 7.8 × 10−5 ± 4.1 × 10−5 mol/L; HSD + MEL: 8.7 × 10−5 ± 5.1 × 10−5 mol/L; p = 0.55) nor free radical number (HSD + PL: 8.0 × 1015 ± 4.4 × 1015; HSD + MEL: 9.0 × 1015 ± 4.9 × 1015; p = 0.51) were different between conditions. Melatonin supplementation did not alter vascular function or ROS levels while on a HSD in this sample of young healthyItem Sex differences in microvascular function and arterial hemodynamics in nondialysis chronic kidney disease(American Journal of Physiology - Heart and Circulatory Physiology, 2022-12-01) Kirkman, Danielle L.; Ramick, Meghan G.; Muth, Bryce J.; Stock, Joseph M.; Townsend, Raymond R.; Edwards, David G.Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD). Abnormal arterial hemodynamics contribute to CVD, a relationship that can be mediated by microvascular dysfunction. The purpose of this study was to investigate potential sex differences in arterial hemodynamics and microvascular dysfunction in patients with stages 3 to 4 CKD. Vascular function was assessed in 22 male (mean ± SD; age, 56 ± 13 yr) and 10 female (age, 63 ± 9 yr) patients. Arterial hemodynamics were acquired with combined tonometry and oscillometry. Skin blood flow was used as a model of microvascular function. Participants were instrumented with three microdialysis fibers for the delivery of 1) Ringer’s solution; 2) superoxide dismutase mimetic, Tempol; and 3) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin. Blood flow was measured via laser-Doppler flowmetry during standardized local heating (42°C). Central pulse pressure (mean ± SE; 62 ± 9 vs. 46 ± 3 mmHg; P = 0.01) and augmentation index (36 ± 3 vs. 26 ± 3%; P = 0.03) were higher in females. There was a trend for higher central systolic pressures in females (146 ± 9 vs. 131 ± 3 mmHg; P = 0.06). Females reported higher forward (39 ± 4 vs. 29 ± 2 mmHg; P = 0.004) and reflected (27 ± 3 vs. 19 ± 1 mmHg; P < 0.001) wave amplitudes. Cutaneous vascular function was impaired in females compared with males (77 ± 3 vs. 89 ± 1%, P = 0.001). Microvascular function was improved following the delivery of Tempol and apocynin in females but not in males. Female patients with CKD had poorer central hemodynamics and reduced microvascular function compared with their male counterparts. Oxidative stress may contribute to lower microvascular function observed in females. NEW & NOTEWORTHY There are limited data regarding the physiological mechanisms of potential sex differences in central hemodynamics and vascular function in chronic kidney disease (CKD). We report that older female patients with nondialysis CKD have higher central pulse pressures compared with male patients with CKD. In addition, older females with CKD have lower microvascular function compared with their male counterparts, and oxidative stress contributes to the lower microvascular function in older female patients with CKD.