Influence of fasting on the effects of diazoxide in the ischemic-reperfused rat heart.
This investigation aimed to assess whether the mitochondrial ATP-sensitive potassium channel opener diazoxide could reproduce the protection conferred by ischemic preconditioning and to ascertain whether its effects are associated with changes in glycogen breakdown and glycolytic activity. Hearts of fed and 24-h fasted rats were perfused with 10 mM glucose containing medium and exposed to 25 min no-flow ischemia plus 30 min reperfusion. Diazoxide (10 microM) perfusion was begun 10 min before ischemia and continued throughout the experiment. Fasting accelerated reperfusion recovery of contraction, reduced the post-ischemic contracture and decreased lactate accumulation during ischemia but had no effects on glycogen levels and cellular viability. Diazoxide, did not affect glycogen catabolism but improved reperfusion recovery of contraction. Furthermore, diazoxide reduced ischemic lactate accumulation and contracture amplitude only in the fed group whereas it improved cell viability in the fed and fasted groups. These data indicate that: 1) reduced lactate production which may attenuate myocyte acidification might explain, at least in part, the beneficial effects of diazoxide on mechanical function, although data obtained with the fasted rat hearts indicate that other mechanisms must be involved as well; 2) the reduction of lactate production occurring in the fed group, does not seem to be related to glycogenolysis; and 3) since diazoxide improved cell viability in the fasted rat group where it did not reduce glycolytic activity, other mechanisms may be responsible for this cytoprotective effect.
Marina Prendes
M G
MG
Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires 1028 Buenos Aires, Argentina. gmarina@ffyb.uba.ar
Rastelli
A H
AH
Astudilla
C
C
Fernández
M A
MA
Martínez
M
M
Perazzo
J C
JC
Testoni
G
G
Savino
E A
EA
Varela
A
A
D000818:Animals; D003981:Diazoxide / Q000494:pharmacology*; D005215:Fasting; D005260:Female; D019194:Ischemic Preconditioning; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D015221:Potassium Channels; D003981:Diazoxide