New Horizons in Translational Medicine,2017,2,1,33.
Introduction: Metabolic syndrome (MetS) is associated with inactivation of coronary endothelial small/intermediate (SKCa/IKCa) conductance cal- cium-activated potassium channels and dysregulation of coronary arter- iolar endothelial function in animals and humans. We investigated the effects of cardioplegia-ischemia/reperfusion (I/R) and NS309 pretreatment on the in-vitro coronary arteriolar responses to endothelium-dependent vasodilators substance P and ADP in pigs with or without MetS. Case description: The MetS pigs were developed by feeding with a hyper-caloric, fat/cholesterol diet and the control animals fed with a regular diet for 12 weeks (n 1⁄4 8/group). Coronary arterioles (90-180 micrometers in diameter) were dissected from the harvested left ventricle tissue sample of pigs with and without MetS. The changes in diameter were measured with video microscopy. Microvessel was perfused in the presence or absence of selective SKCa/IKCa activator NS309 (10-5M). The in- vitro coronary arterioles were then subjected to 60 minutes of cardio- plegia-hypoxia (15°C) and 60 minutes of re-oxygenation. Results and Conclusions: At the end of reperfusion, the microvessel was treated with the endothelium-dependent vasodilators substance P and ADP. The relaxation responses to the substance P and ADP after cardioplegia- I/R were significantly decreased in MetS vessels versus control (Lean), respectively (Po0.05), indicating MetS causes more impairment of endo- thelium-dependent-relaxation as compared with controls (Lean). Further- more, pre-treating the MetS or control (lean) pig-microvessels with the SKCa/ IKCa activator NS309 (10-5M) significantly improved the recovery of coronary endothelial function showing increased response to substance P and ADP as compared with no pretreatment alone (Po0.05), but this protective effect is more pronounced in lean-pigs than that of MetS pigs (Po0.05). Take home message: This study demonstrates that cardioplegic- ischemia/reperfusion impairs endothelial function and inactivation of endothelial SKCa/IKCa channels of the coronary microcirculation in the setting of metabolic syndrome. AHA Grant–in–Aid (15GRNT23230014) supported the work.