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Oxidative Stress and Ca 2+ Sparks in Pulmonary Arterial Myocytes of High Altitude Acclimatized Sheep
Author(s) -
Moral Elena,
Romero Monica,
Puglisi Jose,
Bers Donald,
Izu Leighton,
Longo Lawrence,
Wilson Sean
Publication year - 2015
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.29.1_supplement.662.3
Subject(s) - oxidative stress , ryanodine receptor , myocyte , chemistry , hypoxic pulmonary vasoconstriction , oxidative phosphorylation , vasoconstriction , medicine , calcium , endocrinology , pharmacology , biology , biochemistry
High altitude (HA) can cause pulmonary hypertension and deregulate Ca 2+ spark activity, which is due to local ryanodine receptor (RYR) activation and important to hypoxic‐induced pulmonary vasoconstriction (HPV). HA also increases oxidative stress, which can impair Ca 2+ spark activity. We tested the hypothesis that HA alters the impact of oxidative stress on Ca 2+ spark activity in pulmonary arterial (PA) myocytes from low altitude (LA; 335m) and HA acclimatized adult sheep (~3,800m for <100 days). Ca 2+ sparks were recorded using line‐scan confocal imaging of the Ca 2+ indicator Fluo‐4. Oxidative stress was elevated with tert‐butyl H 2 O 2 (TbH 2 O 2 ) or reduced with the antioxidant N‐Acetyl‐Cysteine (NAC). Ca 2+ spark activity and spatial‐temporal properties were analyzed with custom designed software (SparkLab). Oxidative stress decreased Ca 2+ spark frequency in both LA and HA myocytes. NAC decreased frequency in HA but not LA myocytes. Spatial aspects of LA Ca 2+ sparks were increased by both TbH 2 O 2 and NAC, while HA decreased spatial aspects to TbH 2 O 2 . Temporal aspects in LA and HA were increased by NAC and TbH 2 O 2 . The alterations in Ca 2+ spark activity in PA myocytes from LA and HA sheep support the premise that oxidative stress contributes to aberrant Ca 2+ signaling seen following HA. Because RYRs are important to HPV, decreased Ca 2+ spark activity following NAC in HA animals may indicate antioxidants can reduce pulmonary vascular pressures due to HA. This supports studies focused on resolving the mechanisms important to how HA mediated oxidative stress effects Ca 2+ signaling (NIH and NSF support).