Difference in the mechanisms for compensating ischemic acidosis in diabetic rat hearts.
To elucidate the difference in the mechanisms for alkalization during ischemic acidosis between diabetic and non-diabetic hearts, intracellular pH (pHi) was measured by phosphorus-31 magnetic resonance spectroscopy. Diabetes was induced by the injection of streptozotocin. The accumulation of proton ion (DeltaH+) during 15 min global ischemia at 37 degreesC was calculated from pH i. There were no significant differences in DeltaH+ between diabetic (DM: 0. 54+/-0.03 micromol/l,n=6; mean+/-s.e.m.) and non-DM hearts (0.57+/-0.04, n=6), when perfused with bicarbonate buffer. However, perfusion with HEPES buffer revealed a significant increase of DeltaH+ in DM (0.85+/-0.07, n=5) compared with non-DM (0.61+/-0.06, n=5P<0.05). On the contrary, the addition of a Na+/H+ exchange inhibitor (EIPA; 1 micromol/l) to bicarbonate buffer significantly increased DeltaH+ in non-DM (1.09+/-0.10, n=4) compared with DM (0.71+/-0.03, n=5P<0.01). Perfusion with HEPES buffer and EIPA equally increased DeltaH+ in both groups (DM 1.13+/-0.13, n=4; non-DM 1.15+/-0.14, n=4). Thus, the activity of Na+/H+ exchanger during ischemic acidosis, assessed as the increase of DeltaH+ induced by addition of EIPA to bicarbonate buffer, was higher in non-DM (0.52) than DM (0.17). In contrast, the contribution of bicarbonate-dependent systems evaluated by the deference of DeltaH+ between the bicarbonate buffer and the HEPES buffer was markedly bigger in DM (0.31) than non-DM (0.04). These results indicate that Na+/H+ exchange is a major mechanism to compensate ischemic acidosis in non-DM hearts, whereas bicarbonate-dependent systems compensate the depressed activity of Na+/H+ exchange in DM.
Kusuoka
H
H
Division of Tracer Kinetics, Biomedical Research Center, Suita, Osaka, Japan.
Matsuda
S
S
Ishikawa
M
M
Koga
K
K
Mori
T
T
Yamaguchi
H
H
Nishimura
T
T
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications* / Q000378:metabolism*; D015425:Myocardial Reperfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D001639:Bicarbonates; D017923:Sodium-Hydrogen Exchangers