TY - JOUR
T1 - Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation
AU - Borbouse, Léna
AU - Dick, Gregory M.
AU - Payne, Gregory A.
AU - Berwick, Zachary C.
AU - Neeb, Zachary P.
AU - Alloosh, Mouhamad
AU - Bratz, Ian N.
AU - Sturek, Michael
AU - Tune, Johnathan D.
PY - 2010/4
Y1 - 2010/4
N2 - This investigation tested the hypothesis that metabolic syndrome decreases the relative contribution of specific K+ channels to coronary reactive hyperemia. Ca2+-activated (BKCa), voltage-activated (KV), and ATP-dependent (KATP) K + channels were investigated. Studies were conducted in anesthetized miniature Ossabaw swine fed a normal maintenance diet (11% kcal from fat) or an excess calorie atherogenic diet (43% kcal from fat, 2% cholesterol, 20% kcal from fructose) for 20 wk. The latter diet induces metabolic syndrome, increasing body weight, fasting glucose, total cholesterol, and triglyceride levels. Ischemic vasodilation was determined by the coronary flow response to a 15-s occlusion before and after cumulative administration of antagonists for BK Ca (penitrem A; 10 μg/kg iv), KV (4-aminopyridine; 0.3 mg/kg iv) and KATP (glibenclamide; 1 mg/kg iv) channels. Coronary reactive hyperemia was diminished by metabolic syndrome as the repayment of flow debt was reduced ∼30% compared with lean swine. Inhibition of BK Ca channels had no effect on reactive hyperemia in either lean or metabolic syndrome swine. Subsequent inhibition of KV channels significantly reduced the repayment of flow debt (∼25%) in both lean and metabolic syndrome swine. Additional blockade of KATP channels further diminished (∼45%) the repayment of flow debt in lean but not metabolic syndrome swine. These data indicate that the metabolic syndrome impairs coronary vasodilation in response to cardiac ischemia via reductions in the contribution of K+ channels to reactive hyperemia.
AB - This investigation tested the hypothesis that metabolic syndrome decreases the relative contribution of specific K+ channels to coronary reactive hyperemia. Ca2+-activated (BKCa), voltage-activated (KV), and ATP-dependent (KATP) K + channels were investigated. Studies were conducted in anesthetized miniature Ossabaw swine fed a normal maintenance diet (11% kcal from fat) or an excess calorie atherogenic diet (43% kcal from fat, 2% cholesterol, 20% kcal from fructose) for 20 wk. The latter diet induces metabolic syndrome, increasing body weight, fasting glucose, total cholesterol, and triglyceride levels. Ischemic vasodilation was determined by the coronary flow response to a 15-s occlusion before and after cumulative administration of antagonists for BK Ca (penitrem A; 10 μg/kg iv), KV (4-aminopyridine; 0.3 mg/kg iv) and KATP (glibenclamide; 1 mg/kg iv) channels. Coronary reactive hyperemia was diminished by metabolic syndrome as the repayment of flow debt was reduced ∼30% compared with lean swine. Inhibition of BK Ca channels had no effect on reactive hyperemia in either lean or metabolic syndrome swine. Subsequent inhibition of KV channels significantly reduced the repayment of flow debt (∼25%) in both lean and metabolic syndrome swine. Additional blockade of KATP channels further diminished (∼45%) the repayment of flow debt in lean but not metabolic syndrome swine. These data indicate that the metabolic syndrome impairs coronary vasodilation in response to cardiac ischemia via reductions in the contribution of K+ channels to reactive hyperemia.
KW - Adenosine triphosphate-dependent potassium channels
KW - Calcium-activated potassium channels
KW - Coronary reactive hyperemia
KW - Ossabaw miniature swine
KW - Type 2 diabetes
KW - Voltage-activated potassium channels
UR - http://www.scopus.com/inward/record.url?scp=77949735233&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00888.2009
DO - 10.1152/ajpheart.00888.2009
M3 - Article
C2 - 20118408
AN - SCOPUS:77949735233
SN - 0363-6135
VL - 298
SP - H1182-H1189
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 4
ER -