Transmigration routes and a delayed systemic hypotension in rats after intraperitoneal injection of endotoxin from Escherichia coli.
An intraperitoneal injection of endotoxin (ETX; 3 mg/kg) to rats caused gradual decrease in the systemic arterial blood pressure for up to 3 hr, together with decrease in heart rate, increase in hematocrit, and changes in the core temperature (an initial increase and a subsequent decrease). Pretreatment of rats with indomethacin (10 mg/kg, p.o.) prevented the decrease in the systemic blood pressure and the changes in other three parameters. The intraperitoneal injection of ETX also induced a gradual increase in exudation of plasma for up to 3 hr, with increased levels of prostaglandin (PG) E2 and 6-keto-PGF1 alpha in the peritoneal exudate. Indomethacin inhibited the exudation of plasma. The levels of ETX in the arterial and portal venous plasmas began to increase 5 min after the intraperitoneal injection of ETX, and reached levels on the order of micrograms per milliliter plasma 10-20 min after the injection. The levels of ETX in the right and left thoracic lymph nodes, but not in the mesenteric lymph nodes, increased in parallel with those in the systemic arterial plasma. In conclusion, the delayed hypotension may be attributable to the mesenteric vasodilatation induced by PGs generated in the peritoneal cavity, and the ETX injected entered the systemic circulation mainly through lymphatic vessels, but in the initial stage, a part of ETX may be transmigrated into portal vein through damaged intestine.
Sugimoto
K
K
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Kawamura
M
M
Katori
M
M
Shindo
M
M
Ohwada
T
T
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D015232:Dinoprostone / Q000032:analysis; D004731:Endotoxins / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D004926:Escherichia coli / Q000472:pathogenicity*; D005122:Exudates and Transudates / Q000737:chemistry / Q000187:drug effects; D006400:Hematocrit; D007022:Hypotension / Q000139:chemically induced*; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007422:Intestines / Q000187:drug effects; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010538:Peritonitis / Q000139:chemically induced; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D011738:Pyrilamine; D015232:Dinoprostone; D007213:Indomethacin; D008784:Methysergide