The effects of the calcium entry blockers, nilvadipine and nitrendipine, on endotoxin-induced disseminated intravascular coagulation.
We previously reported that calcium entry blockers (CEBs) protected against endotoxin-induced mortality in rats. In this investigation, the i.v. injection of endotoxin (ETX) in control awake male Wistar rats was found to produce pathophysiological changes indicative of disseminated intravascular coagulation (DIC). The latter included increased serum fibrin (ogen) degradation products (FDP), decreased plasma fibrinogen, reduced blood platelet count as well as microscopic findings of fibrin microthrombi in small blood vessels of visceral organs. Gross pathological examination revealed pronounced hemorrhagic congestion of the gastrointestinal tract and petechial and ecchymotic hemorrhages in other visceral organs. Pretreatment with the CEBs, nilvadipine (FR 34235) and nitrendipine, inhibited the elevation in serum FDP and decrease in plasma fibrinogen but did not prevent the thrombocytopenia produced by ETX. The gross pathological manifestations of DIC were also inhibited by pretreatment with the CEBs. The results suggest that the protective effect of CEBs against endotoxin-induced mortality in rats may be related to inhibition of DIC caused by the lipopolysaccharide.
Lee
H C
HC
Department of Pharmacology, John A. Burns School of Medicine, University of Hawaii, Honolulu 96822.
Hardman
J M
JM
Lum
B K
BK
D000372:Agglutination Tests; D000818:Animals; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000209:etiology / Q000473:pathology; D004731:Endotoxins / Q000633:toxicity*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009568:Nitrendipine / Q000008:administration & dosage / Q000494:pharmacology*; D010976:Platelet Count; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains
D004731:Endotoxins; D005338:Fibrin Fibrinogen Degradation Products; C035100:nilvadipine; D005340:Fibrinogen; D009568:Nitrendipine; D009543:Nifedipine