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Metabolic syndrome abolishes A 2A receptor and K ATP channel involvement in coronary arteriolar dilation to adenosine in Ossabaw swine
Author(s) -
Bender Shawn B.,
Sturek Michael,
Laughlin M. Harold
Publication year - 2008
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.22.1_supplement.1226.26
Subject(s) - adenosine , medicine , endocrinology , adenosine receptor , glibenclamide , receptor , potassium channel , contraction (grammar) , blockade , dilation (metric space) , chemistry , adenosine a1 receptor , diabetes mellitus , agonist , mathematics , combinatorics
Reduced coronary flow reserve to adenosine and altered adenosine receptor expression/signaling are common in diabetes and metabolic syndrome (MetS). We hypothesized that reduced adenosine 2A (A 2A ), but not 2B (A 2B ), receptor and ATP‐sensitive (K ATP ) and voltage‐gated (K v ) potassium channel function contribute to reduced coronary arteriolar dilation to 2‐chloroadenosine (2‐CADO) in MetS. Swine were fed control (C) or excess kcal atherogenic diet for 9 wk to study early stage MetS. Dose‐ response curves to 2‐CADO in isolated coronary arterioles were performed in the absence or presence of ZM241385 and/or alloxazine to inhibit A 2A or A 2B receptors, respectively. Responses were also examined in the presence of glibenclamide or 4‐aminopyridine to inhibit K ATP or K v channels, respectively. Dilation to 2‐CADO was similar in C and MetS swine. A 2A and A 2A+2B , but not A 2B , receptor blockade similarly reduced maximal 2‐CADO dilation in C arterioles. Conversely, A 2A or A 2B blockade had no effect while A 2A+2B inhibition right shifted the curve in MetS arterioles. K ATP and K v inhibition right shifted the curve in C, while only K v inhibition did so in MetS arterioles. Dilation to SNP was unchanged. These data suggest that MetS disrupts pathways involved in coronary dilation to adenosine, which are compensated for, thereby preserving arteriolar dilation to adenosine in MetS. Support: HL52490, AR048523, RR013223, HL062552.