Hemodynamic and metabolic effects of intravenous formyl-methionyl-leucyl-phenylalanine (FMLP) in rabbits.
We have studied the role of neutrophils and the effects of the chemotactic factor FMLP, using normal, neutropenic (after cyclophosphamide treatment) and C5a desArg-treated unanesthetized rabbits. The intravenous administration of FMLP in normal animals induces transient and dose-dependent hypotension, neutropenia and thrombocytopenia, with a maximal response in 3 minutes. When a bolus of 5 x 10(-9) moles FMLP was administered, maximal arterial hypotension (40 +/- 1.1 v.s. 90 +/- 1.1 mmHg in the controls, P < 0.001) accompanied by a significant increase in central venous pressure (0.89 +/- 0.9 v.s. -2.2 +/- 0.7 mmHg in the controls, P < 0.01) and a decrease in systemic vascular resistance (90 +/- 15.6 v.s 187 +/- 16.4 mmHg/L/min, P < 0.005). Plasma pH and bicarbonate were significantly reduced, with a parallel increase in plasma lactate levels. A similar reduction of arterial blood pressure was also noted in neutropenic animals (31 +/- 3% of pretreatment levels respectively). C5a des Arg caused neutropenia similar to that seen after 5 x 10(-9) moles FMLP (120 +/- 60/mm3 and 170 +/- 25/mm3 respectively), but it did not induce hypotension. These data suggest that simple neutrophil activation is not the mechanism of the FMLP-induced hypotension and that this chemotactic factor may interact with other cell types to produce its effects.
Jonsson
M
M
Department of Medicine, Veterans Administration Medical Center, Augusta, GA 30904-6285, USA.
Tzanela
M
M
Kolbeck
R C
RC
McCormick
J R
JR
D000818:Animals; D001784:Blood Gas Analysis; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D015937:Complement C5a, des-Arginine / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007773:Lactates / Q000097:blood; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism / Q000494:pharmacology*; D009503:Neutropenia / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011817:Rabbits
D015937:Complement C5a, des-Arginine; D007773:Lactates; D009240:N-Formylmethionine Leucyl-Phenylalanine