Chronic ethanol consumption exacerbates microcirculatory damage in rat mesentery after reperfusion.
Although the negative effect of excessive alcohol consumption on later stressful events has long been recognized, pathophysiological mechanisms are incompletely understood. We examined possible roles of oxygen radicals and glutathione content in mesenteric venules of chronically ethanol-fed rats exposed to ischemia-reperfusion. Changes in microvascular hemodynamics, such as red blood cell (RBC) velocity, leukocyte adherence, and albumin extravasation, were monitored in postcapillary venules by intravital fluorescence microscopy. Chronic ethanol feeding significantly exaggerated the magnitude of the decrease in RBC velocity, the increased number of adherent leukocytes, and increased albumin leakage elicited by 10 min of ischemia followed by 30 min of reperfusion. Oxidative stress in the endothelium of venules monitored by dihydrorhodamine 123 (DHR) fluorescence was more severe in rats fed ethanol chronically. Both superoxide dismutase and N-acetyl-L-cysteine, which is known to increase glutathione content, reduced the ischemia-reperfusion-induced decrease in RBC velocity, the number of adherent leukocytes, and the increase in albumin leakage, as well as oxidative activation of DHR. This suggests that the increased reperfusion-induced microvascular disturbances in the mesenteric venules of rats fed ethanol chronically are significantly correlated with excessive production of oxygen-derived free radicals and decreased glutathione synthesis.
Han
J Y
JY
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Miura
S
S
Akiba
Y
Y
Higuchi
H
H
Kato
S
S
Suzuki
H
H
Yokoyama
H
H
Ishii
H
H
D000437:Alcoholism / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001783:Blood Flow Velocity; D002448:Cell Adhesion; D003912:Dextrins; D004912:Erythrocytes / Q000502:physiology; D005456:Fluorescent Dyes; D006439:Hemodynamics; D007511:Ischemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D012235:Rhodamines; D012709:Serum Albumin / Q000378:metabolism; D013152:Splanchnic Circulation / Q000502:physiology*; D014699:Venules / Q000473:pathology / Q000503:physiopathology
D003912:Dextrins; D005456:Fluorescent Dyes; D012235:Rhodamines; D012709:Serum Albumin; C058319:dihydrorhodamine 123