Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation

Léna Borbouse, Gregory M. Dick, Gregory A. Payne, Zachary C. Berwick, Zachary P. Neeb, Mouhamad Alloosh, Ian N. Bratz, Michael Sturek, Johnathan Tune

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume298
Issue number4
DOIs
StatePublished - Apr 2010

Fingerprint

Vasodilation
Hyperemia
Swine
Adenosine Triphosphate
Fats
Cholesterol
Atherogenic Diet
Large-Conductance Calcium-Activated Potassium Channels
Diet
Miniature Swine
4-Aminopyridine
Glyburide
Fructose
Fasting
Triglycerides
Ischemia
Body Weight
Maintenance
Glucose

Keywords

  • Adenosine triphosphate-dependent potassium channels
  • Calcium-activated potassium channels
  • Coronary reactive hyperemia
  • Ossabaw miniature swine
  • Type 2 diabetes
  • Voltage-activated potassium channels

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation. / Borbouse, Léna; Dick, Gregory M.; Payne, Gregory A.; Berwick, Zachary C.; Neeb, Zachary P.; Alloosh, Mouhamad; Bratz, Ian N.; Sturek, Michael; Tune, Johnathan.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 298, No. 4, 04.2010.

Research output: Contribution to journalArticle

Borbouse, Léna ; Dick, Gregory M. ; Payne, Gregory A. ; Berwick, Zachary C. ; Neeb, Zachary P. ; Alloosh, Mouhamad ; Bratz, Ian N. ; Sturek, Michael ; Tune, Johnathan. / Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation. In: American Journal of Physiology - Heart and Circulatory Physiology. 2010 ; Vol. 298, No. 4.
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AU - Dick, Gregory M.

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AU - Berwick, Zachary C.

AU - Neeb, Zachary P.

AU - Alloosh, Mouhamad

AU - Bratz, Ian N.

AU - Sturek, Michael

AU - Tune, Johnathan

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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.

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