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Am J Physiol Regul Integr Comp Physiol 253: R549-R554, 1987;
0363-6119/87 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 253, Issue 4 549-R554, Copyright © 1987 by American Physiological Society

ARTICLES

Effect of diltiazem on altered cellular calcium regulation during endotoxic shock

M. M. Sayeed and S. R. Maitra
Department of Physiology, Loyola University Stritch School of Medicine, Maywood, Illinois 60153.

Cellular free and exchangeable Ca2+ were quantitated in livers of rats injected with saline (control), Salmonella enteritidis endotoxin (20 mg/kg), or diltiazem (0.8-1.2 mg/kg) plus the endotoxin (20 mg/kg). Injection of endotoxin alone resulted in signs of endotoxic shock in animals 5 h later. All rats were killed 5 h postinjection, and their livers were excised. Hepatocytes were prepared for the measurement of cytosolic [Ca2+] under basal and hormone-stimulated (1 and 10 microM epinephrine) conditions by means of quin 2 fluorescence technique. Liver slices were labeled with 45Ca, and the radioactivity was washed out to determine cellular exchangeable Ca2+. The apparent basal level of cytosolic Ca2+ in endotoxic rat hepatocytes [525 +/- 92 (SE) nM] was significantly (P less than 0.05) higher than in controls (146 +/- 23). A significant increase in the basal [Ca2+] occurred after stimulation with epinephrine in controls but not in endotoxic rat hepatocytes. In the endotoxic rats receiving diltiazem, basal [Ca2+] was significantly lower than in rats given endotoxin alone, and a significant elevation of cytosolic [Ca2+] with epinephrine also occurred. The cellular exchangeable Ca2+ in endotoxic rats (564 +/- 27 nmol/g) was significantly higher than in controls (427 +/- 23). Diltiazem treatment of endotoxic rats restored the exchangeable Ca2+ level to that found in controls. The endotoxic accumulation of cellular Ca2+ and its restoration toward control levels by diltiazem could be due to catecholamine-mediated Ca2+ influx and its blockade by diltiazem.


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