rBPI23 attenuates endotoxin-induced cardiovascular depression in awake rabbits.
We determined the effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) on hemodynamic and renal sympathetic responses to lethal endotoxemia in unanesthetized rabbits. Endotoxin was continuously infused intravenously (200 micrograms/kg/h) over 120 min with simultaneous infusion of either rBPI23 (3 mg/kg bolus followed by 6 mg/kg/h over 120 min; n = 6) or thaumatin (the same dose as rBPI23), a control cationic protein with a molecular weight and isoelectric point similar to that of rBPI23 (n = 9). Tissue blood flow was also determined using colored microspheres to the left ventricle, renal cortex, liver, and skeletal muscle. Seven of nine animals treated with endotoxin and thaumatin died between 45 and 120 min after start of the infusion, whereas all animals with rBPI23 treatment were alive throughout the entire 2 h experimental period. A transient increase in renal sympathetic nerve activity was observed in the thaumatin-treated animals followed by sympathoinhibition with concomitant decreases in heart rate, blood pressure, and cardiac output. Tissue blood flow to all measured organs gradually decreased in animals receiving endotoxin and thaumatin. However, rBPI23 abolished all these deleterious responses to endotoxin. In conclusion, rBPI23 attenuates the acute lethal sympathoinhibitory and hemodynamic effects of endotoxemia in awake rabbits.
Koyama
S
S
Department of Physiology, Shinshu University School of Medicine, Nagano 390, Japan.
Shibamoto
T
T
Ammons
W S
WS
Saeki
Y
Y
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D001783:Blood Flow Velocity / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D004731:Endotoxins / Q000633:toxicity*; D006339:Heart Rate / Q000502:physiology; D007447:Invertebrate Hormones / Q000494:pharmacology*; D007668:Kidney / Q000294:innervation* / Q000503:physiopathology; D008565:Membrane Proteins / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology
D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D004731:Endotoxins; D007447:Invertebrate Hormones; D008565:Membrane Proteins; D011994:Recombinant Proteins; C034705:antilipopolysaccharide factor (Limulus); C025357:endotoxin binding proteins