Abstract 17342: Decreased Relaxation Response of Coronary Arterioles to Calcium-Activated-Potassium -Channel Activators in Diabetic patients
Background: We investigated the effect of diabetes on coronary arteriolar responses to the large conductance of calcium-activated potassium channel (BKCa) activator NS1619, and small/intermediate conductance of calcium-activated potassium channel (SKCa/IKCa) opener NS309.
Methods and Results: Pre-CP/CPB coronary arterioles (90 -150 micrometers in diameter) were harvested from diabetic (HbA1C > 9.0) and non-diabetic patients (HbA1C < 6.0) during CABG surgery (n = 8/group). In-vitro relaxation response of pre-contracted arterioles was examined in the presence of selective BKCa activator NS1619 or selective SKCa/IKCa activator NS309. The distribution of the BKCa, SKCa and IKCa in the atrial microvasculature was examined by immuno-histochemistry. Our results indicate that diabetes significantly reduced the coronary arteriolar response to the BKCa activator NS 1619 or the SKCa/IKCa activator NS309 compared to the respective responses of non-diabetic vessels (P <0.05 vs. non-diabetes). In addition, the relaxation response of diabetic arterioles to NS309 was prevented by denudation of endothelium (P = 0.001 vs. endothelium-intact), but the response to NS1619 was not affected by endothelium denudation, suggesting that NS309-induced response is endothelium-dependent in the diabetic arterioles. There were no significant differences in the distribution of BKCa, SKCa and IKCa in the coronary microvesels.
Conclusion: Diabetes may be associated with inactivation of coronary smooth muscle BKCa channels and endothelial SKCa/IKCa channels, which may contribute to arteriolar smooth muscle and endothelial dysfunction of diabetic patients.
- Diabetes mellitus
- Vasodilator agents
- Coronary microcirculation
- Endothelium-derived relaxing factor
- Ion channels
Author Disclosures: J. Feng: None. Y. Liu: None. A. Singh: None. A. Ehsan: None. F. Sellke: None.
- © 2014 by American Heart Association, Inc.