Relaxation of Coronary Smooth Muscle By Dobutamine

Dobutamine, a non-selective β1/β2-adrenergic receptor agonist, is commonly used to increase cardiac output and treat heart failure. While its primary actions are attributed to stimulation of cardiac muscle, dobutamine may also directly influence coronary vascular tone. We tested the hypothesis that dobutamine relaxes coronary smooth muscle, in part, through the activation of KATP and BK channels. Left circumflex coronary artery rings were isolated from male and female Yorkshire swine and studied using wire myography. Data were collected through isometric tension recordings in order to calculate percent relaxation to quantify responses. Rings were contracted with the synthetic thromboxane U46619, and concentration-dependent relaxation responses to dobutamine were recorded. Endothelial dependence was evaluated by comparing responses in intact and denuded arteries, and K + channel involvement was assessed using pharmacological blockers. Dobutamine produced concentration-dependent relaxation of coronary smooth muscle that was unaffected by endothelial removal, indicating an endothelium-independent mechanism. Additionally, hyperpolarization of K + was initiated by increasing extracellular K + to disrupt the K + gradient. The response reduced relaxation by ~40%, suggesting involvement of membrane hyperpolarization playing a role in dobutamine-induced relaxation. Blocking BK channels with penitrem A had no effect on dobutamine-mediated relaxation, however, inhibition of KATP channels with PNU significantly reduced relaxation by ~40%. These findings demonstrate that dobutamine directly relaxes coronary smooth muscle independent of the endothelium, likely through activation of KATP channels but not the BK channels. This mechanism may contribute to the coronary vasodilation observed clinically during dobutamine administration and improve understanding of coronary regulation in cardiovascular disease. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.