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Differential AMPK Activation and Contractile Function in Rabbit Leg and Neck Arteries in Response to Oxygen and Glucose Deprivation
Author(s) -
Makinde Toluwalope,
Latham Amauri,
Miner Amy,
Huang Yi,
Sharma Bharti,
Chen Grace,
Barbee Robert,
Ratz Paul
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.803.10
Subject(s) - myograph , ampk , medicine , endocrinology , hypoxia (environmental) , chemistry , protein kinase a , contraction (grammar) , biology , oxygen , kinase , biochemistry , organic chemistry
AMP‐activated protein kinase (AMPK) is a primary metabolic stress sensor. Glucose and O 2 levels change dramatically in hemorrhage and may reduce the ability of arteries to constrict in the compensatory phase. Femoral (FA), saphenous (SA) and carotid arteries (CA) were isolated from euthanized male NZW rabbits. Blood vessels were divided into four treatment groups: control (CTRL; 11.2mM glucose, pO 2 ~150mmHg), zero glucose (0‐GLC), hypoxia (HYP; <10mmHg), or hypoxia plus zero glucose (STARVE). Tissues were either retained at zero external tension (T ze ) or secured in a tissue myograph and adjusted to the optimal length (L o ). At 30, 60, and 120 minutes, tissues at L o were contracted while T ze tissues were quickly frozen and analyzed for phospho‐AMPK and its substrates by western‐blot. 0‐GLC alone was insufficient to cause a “failure” to contract to PE but these did inhibit by ~50% the tonic phase of the SA contraction by 120 mins, a response not seen in the larger FA and CA. 0‐GLC group displayed no significant change in any of the phospho‐proteins assessed at 30, 60 and 120 min. At 30 and 60 min, tissues from the HYP group displayed ~4‐fold increases in AMPK‐pT172 and ACC‐pS79, and a 1.5‐fold increase in Raptor‐pS792. Tissues from the STARVE group displayed a strong 8‐fold increase in AMPK‐pT172, 10‐fold increase in ACC‐pS79 and 2‐fold increase in Raptor‐pS792. These data show that rabbit arteries respond to metabolic stress with increases in AMPK signaling and that small muscular arteries maybe more sensitive to changes in glucose. Support: DOD Grant #W81XWH‐12‐1‐0525