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Aging Impairs Spontaneous Ca 2+ Signaling and Regulation by CGRP in Smooth Muscle Cells of Mouse Mesenteric Arteries
Author(s) -
Boerman Erika M,
Segal Steven S
Publication year - 2016
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.30.1_supplement.945.3
Subject(s) - calcitonin gene related peptide , vasomotor , endocrinology , medicine , mesenteric arteries , vasoconstriction , vasodilation , chemistry , smooth muscle , vascular smooth muscle , neuropeptide , artery , receptor
Advancing age is associated with impaired vasomotor function in resistance arteries. Thus, diminished potency of calcitonin gene‐related peptide (CGRP) coupled with loss of sensory nerve inhibition of sympathetic vasoconstriction contribute to impaired vasodilation in mouse mesenteric arteries (MAs; PMC3607869 ). In light of multiple roles for Ca 2+ signaling in governing vasomotor function, we tested the hypothesis that aging impairs both spontaneous and CGRP‐mediated Ca 2+ signals in smooth muscle cells (SMCs). MAs (n = 14–18) from Young (~4 months) and Old (~24 months) C57BL/6 mice were isolated, pressurized to 100 cm H 2 O and studied at 37°C following loading of SMCs with Fluo‐4 (10 μM, 1h, 37 °C ). With ~15 SMCs per field, under control conditions Young MAs had 9 ± 1 sites producing spontaneous local Ca 2+ events versus 4 ± 1 sites in Old MAs (P<0.05) while the number of SMCs exhibiting spontaneous Ca 2+ waves (7 ± 1) was not different between age groups. Age‐defined EC 50 concentrations of norepinephrine (NE; 167 and 600 nM) reduced local Ca 2+ event sites in Young and Old MAs (to 3 ± 1 and 1 ± 1, respectively; P<0.05) and increased the number of SMCs with Ca 2+ waves in both age groups (to 11 ± 1 and 14 ± 1). In Young but not Old MAs, addition of CGRP (100 nM) restored local Ca 2+ event sites and Ca 2+ waves to control values. Across age groups the frequency (0.6 ± 0.01 Hz), amplitude (1.3 ± 0.01 F/F o ), rise time (73 ± 8 ms), and duration (FDHM, 164 ± 9 ms) of local Ca 2+ events did not differ with age, NE or CGRP treatments. We suggest that the impaired ability of CGRP to restore local Ca 2+ signaling (e.g., as associated with BK channel activation) in SMCs of Old MAs during adrenoreceptor activation contributes to age‐related vascular dysfunction underlying impaired vasodilation. Support or Funding Information NIH F32HL118836 & R37HL041026