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Chronic Intermittent Hypoxia Promotes Glomerular Hyperfiltration, Reductions in Renal Blood Flow, and Upregulation of Renal A2B Receptor Expression
Author(s) -
Kious Kiefer W.,
Twohey Stephanie C.E.,
Keomanivong Faithe E.,
Neidermann Sarah E.,
Dirkman Jacob J.,
Marcus Noah J.
Publication year - 2019
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.2019.33.1_supplement.748.8
Subject(s) - medicine , endocrinology , renal function , renal blood flow , kidney , renal circulation
Background/Significance Sleep apnea (SA) is associated with hypertension and chronic kidney disease. Changes in adenosine signaling associated with chronic intermittent hypoxia (CIH) during apneic episodes may alter glomerular hemodynamics and contribute to hyperfiltration. In addition, increased signaling through the adenosine type 2B receptor (A2B) may promote inflammation and contribute to renal damage and eventual declines in renal function. Hypothesis We hypothesized that short‐term exposure to CIH would promote increased glomerular filtration rate and upregulation of A2B, IL‐6, NGAL, and α‐smooth muscle actin (SMA) expression in the kidney. Methods Adult male Sprague Dawley rats were exposed to 10 days CIH (60 sec. FiO2 10%, 120 sec. FiO2 21%) for 8h/d. Glomerular filtration rate (GFR) was measured transdermally (Medibeacon) pre‐ and post‐CIH, and post‐CIH (or sham) renal blood flow (RBF) was measured using Transonic flow probes (2% isoflurane, FiO2 21% and 10%). Cortical and medullary expression of A2B, IL‐6, NGAL, and α‐smooth muscle actin (SMA) was measured via western blot. Results Weight‐corrected RBF decreased modestly (15%) after 10 days of CIH (1.89±0.13 mL/min/g vs. 1.42±0.16 mL/min/g, p<0.05). In contrast weight‐corrected GFR increased by 80% from pre‐ to post‐CIH measurements (3.1±0.27 mL/min/g vs. 5.5±0.51 mL/min/g, p<0.05). Renal cortical A2B (1.0±0.09 sham vs. 1.42±0.15 CIH, p<0.05) and IL‐6 (1.0±0.11 sham vs. 1.56±0.21 CIH, p<0.05) and medullary NGAL (1.0±0.22 sham vs. 2.68±0.65 CIH, p<0.05) expression was increased in CIH relative to sham tissue. SMA was not significantly different between groups. Conclusions Intermittent hypoxia induces glomerular hyperfiltration and upregulation of renal A2B/pro‐inflammatory pathways, which in turn may precede renal injury. Support or Funding Information Supported by a grant from NHLBI (R15 HL138600‐01 to NJM) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .