Impaired contribution of voltage‐dependent K + channels to ischemic coronary vasodilation in Ossabaw swine with metabolic syndrome

This study assessed the contribution of large conductance Ca 2+ ‐activated (BK Ca ) and voltage‐dependent (K V ) K+ channels to coronary ischemic vasodilation in lean and metabolic syndrome (MetS) Ossabaw swine. Experiments were conducted in anesthetized, open‐chest swine fed a normal maintenance diet or an atherogenic diet over 9 weeks that induces MetS. Ischemic vasodilation was assessed by measuring the reactive hyperemic response to a 15‐second occlusion of the left anterior descending coronary artery. Mean body weight was 36 ± 2 kg in lean (n = 8) and 54 ± 3 kg in MetS (n = 7) swine. BK Ca inhibition with penitrem A (10 μg/kg iv) had no effect on peak coronary blood flow in either lean (2.9 ± 0.3 ml/min/g) or MetS (2.6 ± 0.3 ml/min/g) swine. The duration of the reactive hyperemic response was also unaffected by penitrem A in lean (94 ± 10 sec) and MetS (88 ± 8 sec) swine. Subsequent inhibition of K V channels with 4‐aminopyridine (0.3 mg/kg, iv) significantly reduced the duration of reactive hyperemia in lean (66 ± 5 sec) but not in MetS swine (77 ± 12 sec). These data indicate that BK Ca channels do not contribute to ischemic vasodilation in lean or MetS Ossabaw swine. In addition, our findings reveal that K V channels play a prominent role in coronary ischemic vasodilation in lean, but not MetS, swine suggesting putative mechanisms of ischemic dilation are switched in early obesity and MetS. (Support: HL67804, RR013223, HL062552)