Abstract. Preconditioning ischemia (PI) increases the speed of the initial vasodilatation (vascular preconditioning) of a subsequent coronary reactive hyperemia (CRH) and reduces total hyperemic flow (THF). We investigated whether changes in CRH similar to those induced by PI are obtained with diazoxide, a mitochondrial ATP-sensitive K+ channel opener, and whether diazoxide influences the effects of a subsequent PI on CRH. In anesthetized goats, flow was recorded from the left circumflex coronary artery (LCCA). CRH and PI were obtained with 15-s and 5-min LCCA occlusions, respectively. CRH was studied before and after PI, before and after diazoxide (2.5mg/kg i.v.) as well as before and after PI was induced after diazoxide pre-treatment. After PI, the time to peak (ttp) of CRH and THF decreased by 5113% and 238%, respectively. Diazoxide did not change CRH. After diazoxide and PI, when basal flow had returned to the control level, the ttp of CRH was reduced as after PI alone (4512%), whereas THF was reduced to a greater extent (419% versus 238%; P0.01). In conclusion, PI alters CRH by decreasing THF and reducing the ttp of CRH. Whilst diazoxide does not reproduce the effects of PI on CRH, pre-treatment with diazoxide potentiates the effects of PI on THF.