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Impaired Ca 2+ signaling following acutely elevated glucose in mouse endothelial cell tubes
Author(s) -
Socha Matthew J.,
Domeier Timothy L.,
Sowers James R.,
Segal Steven S.
Publication year - 2013
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.27.1_supplement.678.2
Subject(s) - medicine , endocrinology , endothelium , mannitol , calcium , chemistry , acetylcholine , endothelial dysfunction , endothelial stem cell , biochemistry , in vitro
Calcium signaling is integral to endothelial function and may be altered by hyperglycemia, a hallmark of diabetes. We tested the hypothesis that acute exposure to elevated glucose impairs Ca 2+ signaling of native endothelium from resistance arteries of skeletal muscle. Intact endothelial cell tubes were isolated from superior epigastric arteries of male C57BL/6 mice (3–4 mos). Monitoring Ca 2+ levels during exposure to control (10 mM) or elevated (20 mM) glucose for 30 min had no effect on resting Ca 2+ (Δ fura‐2 ratio: 0.13±0.03 vs. 0.14±0.01, respectively; n=3). After loading with fluo‐4 dye, Ca 2+ responses were evoked with 1 μM acetylcholine (ACh) in physiological solutions with normal (10 mM) and elevated (20 or 30 mM) glucose (with mannitol as an osmotic control) and imaged using spinning‐disc confocal microscopy. Exposure to 20 mM glucose for 30 min diminished peak Ca 2+ responses (F/F 0 ) to ACh (from 3.14±0.27 to 2.11±0.12; n=3, P <0.05) that were otherwise maintained in 10 mM glucose. These reductions in F/F 0 with 20 mM glucose persisted for 1 hr following restoration of 10 mM glucose. Elevating glucose to 30 mM effectively abolished Ca 2+ responses to ACh, which did not recover within 1 hr. Acute exposure to elevated glucose can impair endothelial Ca 2+ signaling in the endothelium of resistance arteries and thereby contribute to endothelial dysfunction in diabetes. (NIH R37HL041026, R01HL086483, F32HL107050)