AJP - Regulatory, Integrative and Comparative Physiology, Vol 263, Issue 3 553-R558, Copyright © 1992 by American Physiological Society
Ca(2+)-related hepatocellular alterations during intra-abdominal sepsis
S. Rose, K. D. Thompson and M. M. Sayeed
Department of Physiology, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
Intra-abdominal sepsis was induced in rats by implanting into their
abdominal cavities fecal-agar pellets impregnated with Escherichia coli and
Bacteroides fragilis. Sham-operated rats received sterile pellets. A group
of sterile- and septic-implanted rats was treated intraperitoneally with
diltiazem (1.2 mg/kg) 8 h after implantations. Septic- and
sterile-implanted rat hepatocytes were loaded with 1) the fluorescent dye
indo-1 to quantify hepatocyte basal and vasopressin (100 nM)-elevated
cytosolic Ca2+ concentration and 2) 45Ca to quantify Ca2+ flux and cellular
content of exchangeable Ca2+. Lipid peroxidation was determined by
measuring conjugated dienes (CD) and thiobarbiturate-reactive substances
(TBA-RS) in liver homogenates. In septic-implanted rats, the basal
cytosolic [Ca2+], cellular exchangeable Ca2+, Ca2+ flux, CD, and TBA-RS
were significantly higher than in sterile-implanted rats. Although
vasopressin caused a significant elevation in cytosolic [Ca2+] in septic
rat hepatocytes, the magnitude of this elevation was significantly smaller
than that found in the sterile group. Diltiazem treatment of septic rats
significantly decreased basal cytosolic [Ca2+], cellular exchangeable Ca2+
content, Ca2+ flux, CD, and TBA-RS. Also, vasopressin-induced increase in
hepatocyte cytosolic [Ca2+] in diltiazem-treated septic rats was
significantly greater than that observed in untreated septic rats. Both
Ca2+ and membrane lipid alterations were attenuated with diltiazem
treatment of septic rats. These results suggest that prevention or
attenuation of Ca2+ channel-mediated Ca2+ influx restores both Ca2+
homeostasis and membrane lipid alteration.
