Mitochondrial ATP-sensitive channel opener does not induce vascular preconditioning, but potentiates the effect of a preconditioning ischemia on coronary reactive hyperemia in the anesthetized goat

Preconditioning ischemia (PI) increases the speed of the initial vasodilata tion (vascular preconditioning) of a subsequent coronary reactive hyperemia (CRH) and reduces total hyperemic flow (THF). We investigated whether chan ges in CRH similar to those induced by PI are obtained with diazoxide, a mi tochondrial ATP-sensitive K+ channel opener., and whether diazoxide influen ces 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 o btained with 15-s and 5-min LCCA occlusions, respectively. CRH was studied before and after PI, before and after diazoxide (2.5 mg/kg i.v.) as well as before and after PI was induced after diazoxide pre-treatment. After PI. t he time to peak (ttp) of CRH and THF decreased by 51 +/- 13% and 23 +/-8%. respectively. Diazoxide did not change CRH. After diazoxide and PI, when ba sal flow had returned to the control level, the ttp of CRH was reduced as a fter PI alone (-45 +/- 12%). whereas THF was reduced to a greater extent (- 41 +/-9% versus -23 +/-8%; P <0.01). In conclusion, PI alters CRH by decrea sing THF and reducing the ttp of CRH. Whilst diazoxide does not reproduce t he effects of PI on CRH, pre-treatment with diazoxide potentiates the effec ts of PI on THF.