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 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 (2.5 mg/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 51+/-13% and 23+/-8%, 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 (-45+/-12%), whereas THF was reduced to a greater extent (-41+/-9% versus -23+/-8%; P<0.01). 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.
Pagliaro
P
P
Dipartimento di Scienze Cliniche e Biologiche dell'Università di Torino, Ospedale S. Luigi, Regione Gonzole, 10043 Orbassano, TO, Italy. pasquale.pagliaro@unito.it
Rastaldo
R
R
Losano
G
G
Gattullo
D
D
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003981:Diazoxide / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006041:Goats; D006940:Hyperemia / Q000503:physiopathology*; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D008928:Mitochondria / Q000378:metabolism*; D012016:Reference Values
D007473:Ion Channels; D000255:Adenosine Triphosphate; D003981:Diazoxide