Mechanisms of intracellular pH regulation during postischemic reperfusion of diabetic rat hearts.
A marked decrease in the activity of the amiloride-sensitive Na+/H+ exchanger has been demonstrated in hearts from streptozotocin (STZ)-induced diabetic rats. The aim of this study was to investigate the contribution of other specific sarcolemmal transport mechanisms to intracellular pH (pHi) recovery upon reperfusion in STZ-induced diabetic rat hearts and their relation to recovery of ventricular function. Isovolumic rat hearts were submitted to a zero-flow ischemic period of 28 min at 37 degrees C and then reperfused for 28 min. The time course of pHi decline during ischemia and of recovery on reperfusion was followed by means of 31P-labeled NMR. The perfusion buffers used were either HEPES or CO2/HCO3-. An HCO3(-)-dependent (amiloride-insensitive) mechanism contributed to pHi recovery after ischemia in the diabetic rat hearts. Even when the Na+/H+ exchanger was blocked by amiloride in nominally HCO3(-)-free solution, a rapid rise in pHi occurred during the first 3 min of reperfusion. The early rise in pHi was reduced by external lactate and inhibited by alpha-cyano-4-hydroxycinnamate. This suggested that a coupled H(+)-lactate efflux may be a major mechanism for acid extrusion in the initial stage of reperfusion. The observation of a higher functional recovery on reperfusion in diabetic hearts is in accordance with previous studies using HCO3- buffer. However, this study shows that a good recovery of function occurred even more rapidly in diabetic hearts receiving HEPES-buffered solution than in those receiving HCO3(-)-buffered solution. This suggests that the HCO3(-)-dependent mechanism of regulation may be depressed in diabetic rat hearts.
Khandoudi
N
N
Laboratoire de Physiologie Cellulaire, Université Paris-XI, Orsay, France.
Bernard
M
M
Cozzone
P
P
Feuvray
D
D
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D006531:HEPES; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D016277:Ventricular Function, Left
D001639:Bicarbonates; D007773:Lactates; D017923:Sodium-Hydrogen Exchangers; D019344:Lactic Acid; D000584:Amiloride; D006531:HEPES