Abstract 18186: The Role of Vascular Smooth Muscle Kv 1.5 Channels in Coronary Metabolic Dilation
The coupling of flow to metabolism in the heart is termed coronary metabolic dilation and enables the proper supply of oxygen and nutrients to sustain cardiac function. Previously we found that mice null for Kv1.5 channels (Kv1.5 -/-) have blunted metabolic dilation, and during high metabolic demand flow is insufficient to meet the needs of the myocardium leading to ischemia. However these mice were null for the channel in all organs, and the expression of Kv1.5 channels in cardiac myocytes, in addition to smooth muscle, is well established. For metabolic dilation, we hypothesized a scheme in which expression of Kv1.5 channels in smooth muscle is key for the process; therefore we determined if expression of the channels only in smooth muscle in the Kv1.5 -/- background would rescue the phenotype of impaired metabolic dilation. We created a line of transgenic mice with doxycycline inducible Kv1.5 channel expression in smooth muscle (SM22 promoter). Expression was induced by 7 days of doxycycline treatment and increased approximately 8-fold over that in wild type mice (WT). Myocardial blood flow was measured using contrast echocardiography. Myocardial blood flow and hemodynamic measurements were done at baseline and during norepinephrine (NE) injection (0.5-5 μg/kg/min) to increase metabolic demand as defined by the pressure rate product (PRP: mean arterial pressure x heart rate). As shown in the figure, blood flow during increased metabolism (PRP) was significantly decreased in Kv1.5-/- mice compared to WT. In the transgenic mice with Kv1.5 overexpression, the coupling of flow to metabolism was increased during NE compared to WT and Kv1.5-/-.
Based on these data, we conclude that expression of Kv1.5 channels in vascular smooth muscle rescues the phenotype of impaired metabolic dilation in the coronary circulation of Kv1.5 -/-.
These results suggest that Kv1.5 channels in vascular smooth muscle are critical for the coupling of flow to metabolism in the heart.
- © 2013 by American Heart Association, Inc.