The small coronary arteries constitute the primary site for regulation of vascular resistance in cardiac muscle and mediate the increased blood flow by metabolic substrates such as adenosine. The goal of the present study was to determine the role of KCNQ-encoded KV channels (KV7 channels) in the passive and active regulation of coronary blood flow in normotensive and hypertensive rats. In normotensive rats different KV7 activators and inhibitors caused dilatation or constriction of left anterior descending coronary arteries, which were not observed in hypertensive rats. In isolated, perfused heart preparations, coronary flow rate increased in response to the KV7 activator (S)-1, and was significantly diminished in the presence of a KV7 inhibitor. The expression levels of KCNQ1-5 and their known accessory KCNE1-5 subunits in coronary arteries were similar in normotensive and hypertensive rats as measured by quantitative PCR. However, KV7.4 protein expression was reduced in hypertensive rats. Application of adenosine or the protein kinase A mediated A2A receptor agonist CGS21680 produced concentration-dependent relaxations of coronary arteries from normotensive rats. However, the effects of adenosine, A2A receptor and CGS21680 were abolished in presence of KV7 inhibitors. KV7 blockers also attenuated the ischemia-induced increase in coronary perfusion in Langendorff studies. Overall, these data suggest that KV7 channels are crucial regulators of coronary blood flow and utilised by adenosine receptor activation to contribute to metabolic hyperemia.