Abstract
Endothelial SKCa and IKCa channels play an important role in the regulation of microvascular tone. We have previously shown that SKA‐31 (naphtho[1,2‐d]thiazole‐2‐ylamine), can inhibit myogenic tone in isolated resistance arteries independent of vasodilatory agonists. We thus hypothesized that acute administration of SKA‐31 may dilate coronary arteries and increase coronary flow. In a Langendorff‐perfused beating rat heart preparation, SKA‐31 dose dependently (0.01–5 μg, single doses) increased total coronary flow (25–30%) in both male (EC50: 0.76 μg) and female (EC50: 0.54 μg) hearts. Increased coronary flow was associated with modest (<20%) increases in left ventricular (LV) pressure and heart rate. Observed changes in flow were more sensitive to SKA‐31 compared to LV pressure and heart rate. The SKA‐31 evoked increases in coronary flow, LV pressure and heart rate were inhibited by a combination of the SKCa blocker apamin and the IKCa blocker TRAM‐34. SKA‐31 evoked vasodilation and associated changes in LV pressure and heart rate were qualitatively comparable to responses evoked by bradykinin (1 μg) and adenosine (10 μg) in the same preparation. Our results demonstrate that SKA‐31 can induce coronary artery dilatation in intact functioning hearts, and further indicate that endothelial SKCa/IKCa channel‐mediated vasorelaxation can be evoked under basal conditions. Supported by CIHR (APB) and NIH (HW).
Published Version
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