Effect of alpha-adrenergic blockage on cellular Ca2+ during endotoxic shock.
The effect of alpha-adrenergic receptor antagonists, phentolamine, and prazosin on cytosolic Ca2+ concentration, [Ca2+]i, was studied in hepatocytes during endotoxic shock. Rats were given intravenous injections of endotoxin (20 mg/kg), phentolamine (3 mg/kg) plus endotoxin (20 mg/kg), or prazosin (5 mg/kg) plus endotoxin (20 mg/kg). They were sacrificed 5 hr later, at which time the endotoxin-injected rats showed signs of shock. Isolated hepatocytes were prepared and employed for the measurement of [Ca2+]i under basal and hormone-stimulated (1 and 10 microM epinephrine) conditions by means of Quin 2 fluorescence technique. The apparent basal level of [Ca2+]i in endotoxic rat hepatocytes (mean +/- SE: 482 +/- 31 nM) was significantly higher (P less than 0.05) than in phentolamine plus endotoxin (242 +/- 73) and prazosin plus endotoxin (240 +/- 43) groups. A significant increase in hepatocyte [Ca2+]i occurred with epinephrine in the phentolamine plus endotoxin and prazosin plus endotoxin groups, but not in the group receiving endotoxin alone. Endotoxic rats showed a mortality rate of 75%, whereas phentolamine plus endotoxin and prazosin plus endotoxin groups showed a mortality rate of 38% and 20% respectively. These data suggest that the protective effect of alpha-adrenergic receptor antagonists during endotoxic shock may be mediated, in part, by attenuating the entrance of Ca2+ into endotoxic liver cells.
Maitra
S R
SR
Department of Surgery, School of Medicine, State University of New York, Stony Brook 11794-8191.
Sayeed
M M
MM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004731:Endotoxins / Q000008:administration & dosage; D004837:Epinephrine; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010646:Phentolamine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000378:metabolism* / Q000401:mortality
D004731:Endotoxins; D002118:Calcium; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine