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Peripheral Blood Mononuclear Cell‐Derived Superoxide Production, Spontaneous Baroreflex Sensitivity, and Vascular Function in Chronic Kidney Disease Patients
Author(s) -
Kaur Jasdeep,
Sabnani Manoj K.,
Stephens Brandi Y.,
Nandadeva Damsara,
Weidanz Jon A.,
Fadel Paul J.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03634
Subject(s) - medicine , oxidative stress , baroreflex , superoxide , kidney disease , arterial stiffness , blood pressure , peripheral blood mononuclear cell , pulse wave velocity , cardiology , renal function , heart rate , endocrinology , nadph oxidase , chemistry , biochemistry , in vitro , enzyme
Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular morbidity and mortality. Previous studies have shown that CKD patients have high oxidative stress, which may be a potential underlying mechanism contributing to vascular dysfunction and impaired baroreflex sensitivity in this patient group. However, the exact mechanism(s) leading to elevated oxidative stress in CKD remains unclear. Peripheral blood mononuclear cells (PBMCs) have been identified as a primary source of NADPH oxidase‐derived superoxide production, leading to elevated systemic oxidative stress. PBMCs can cross the blood brain barrier and increase oxidative stress centrally, which could potentially reduce arterial baroreflex sensitivity (BRS) in these patients. Indeed, there is an emerging body of evidence indicating that elevated oxidative stress impairs BRS. Herein, we tested the hypothesis that CKD patients have greater superoxide production in PBMCs that is associated with impaired vascular function and attenuated BRS. To test this hypothesis, we studied 7 CKD patients stage 3 and 4 (age = 62 ± 3 years, BMI = 35 ± 2 kg/m 2 , estimated glomerular filtration rate (eGFR) = 43 ± 7 ml/min/1.73 m 2 ) and 5 age‐matched controls (age = 57 ± 3 years, BMI = 25 ± 1 kg/m 2 , eGFR = 80 ± 5 ml/min/1.73 m 2 ). PBMCs were isolated from whole blood and intracellular superoxide production in PBMCs was measured using dihydroethidium fluorescence. Resting heart rate (ECG) and arterial blood pressure (finger photoplethysmography) were measured for 10 minutes and spontaneous cardiac BRS was determined using the sequence technique. In addition, central artery stiffness (pulse wave velocity, SphygmoCor) and brachial artery flow‐mediated dilation (duplex Doppler ultrasound) were measured to assess vascular function. CKD patients had significantly elevated PBMC‐derived superoxide production compared to controls (CKD = 32769 ± 4067 vs. controls = 18421 ± 3515 relative fluorescence units; p = 0.03). However, cardiac BRS was not different between the groups (18.2 ± 3.5 in CKD vs 15.4 ± 1.5 ms/mmHg in controls; p = 0.35). Central artery stiffness appeared greater (CKD = 7.8 ± 0.6 vs. controls = 6.3 ± 0.2 m/s; p = 0.07), and endothelial function lower in CKD patients (CKD = 3.5 ± 0.6% vs. controls = 5.8 ± 1.4%; p = 0.19) but neither reached statistical significance in the cohort studied thus far. These preliminary findings suggest that CKD patients exhibit elevated PBMC‐derived superoxide production, which may be one of the mechanisms contributing to impaired vascular function in this population. However, this elevated oxidative stress was not associated with impaired spontaneous cardiac BRS in CKD patients. Support or Funding Information Supported by NIH R01 HL127071