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Aging attenuates spontaneous endothelial Ca 2+ events with altered perivascular nerve function in mouse mesenteric arteries in vivo
Author(s) -
Westcott Erika Boerman,
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.901.3
Subject(s) - phenylephrine , mesenteric arteries , in vivo , endocrinology , chemistry , medicine , vasoconstriction , capsaicin , anatomy , constriction , stimulation , biology , artery , receptor , microbiology and biotechnology , blood pressure
Perivascular nerve activity has been linked to local endothelial cell (EC) Ca 2+ events through α 1 ‐adrenoreceptor (AR) activation, but the effects of aging on perivascular nerves and EC Ca 2+ are unclear. We tested the hypothesis that aging alters local EC Ca 2+ signals in vivo . Superfused (pH, 7.4; 36°C) mesenteric arteries (MAs) of anesthetized Young (3–6 month; n=9) and Old (24–26 month; n=5) Cx40 BAC ‐GCaMP2 mice were imaged (30 frames/s) using spinning disk confocal intravital microscopy. In Young, ECs exhibited spontaneous Ca 2+ events [0.31 ± 0.03 Hz; amplitude (F/F o ): 1.31 ± 0.012; duration: 0.11 ± 0.004 s]. In Old, Ca 2+ events were nearly absent. Electrical field stimulation (EFS) produced frequency‐dependent MA constriction with Old >; Young by ~20%. Blocking sensory nerves (capsaicin, 10 μM) enhanced MA constriction during EFS by ~20% in Young (P < 0.05) but not Old indicating loss of sensory inhibition of sympathetic vasoconstriction in Old. Cumulative activation (1 nM to 10 μM) of α 1 ARs (phenylephrine) but not α 2 ARs (UK14304) exhibited reduced sensitivity (P<0.05) in Old vs. Young. Immunolabeling confirmed sympathetic and sensory nerves were maintained in Old thus functional changes were not due to loss of perivascular innervation. The loss of local EC Ca 2+ signals in Old may reflect α 1 AR desensitization and thereby reduce EC feedback in regulating smooth muscle tone. (NIH R01HL086483, R37HL041026).