Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation.
This investigation tested the hypothesis that metabolic syndrome decreases the relative contribution of specific K(+) channels to coronary reactive hyperemia. Ca(2+)-activated (BK(Ca)), voltage-activated (K(V)), and ATP-dependent (K(ATP)) 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 microg/kg iv), K(V) (4-aminopyridine; 0.3 mg/kg iv) and K(ATP) (glibenclamide; 1 mg/kg iv) channels. Coronary reactive hyperemia was diminished by metabolic syndrome as the repayment of flow debt was reduced approximately 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 K(V) channels significantly reduced the repayment of flow debt ( approximately 25%) in both lean and metabolic syndrome swine. Additional blockade of K(ATP) channels further diminished ( approximately 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.
Borbouse
Léna
L
Dept. of Cellular and Integrative Physiology, Indiana Univ. School of Medicine, Indianapolis, 46202, USA.
Dick
Gregory M
GM
Payne
Gregory A
GA
Berwick
Zachary C
ZC
Neeb
Zachary P
ZP
Alloosh
Mouhamad
M
Bratz
Ian N
IN
Sturek
Michael
M
Tune
Johnathan D
JD
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D006940:Hyperemia / Q000503:physiopathology; D054086:KATP Channels / Q000502:physiology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D013552:Swine; D014463:Ultrasonography; D014664:Vasodilation / Q000502:physiology*
D054086:KATP Channels; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated