Mechanisms of pulmonary vasoconstriction induced by chemotactic peptide FMLP in isolated rabbit lungs.
The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) has been shown to constrict both bronchial and coronary vascular smooth muscle through the action of cyclooxygenase or lipoxygenase products. We observed that intravenous FMLP increased pulmonary vascular resistance (PVR) in isolated buffer-perfused rabbit lungs. FMLP increased the PVR (primarily in the middle segment of the pulmonary vascular bed) at concentrations greater than or equal to 10(-7) M. Maximum vasoconstriction occurred at 5 min and then slowly declined to a level that remained above baseline at 30 min. Tachyphylaxis was observed in response to FMLP. When polymorphonuclear leukocytes (PMNs) were added to the perfusate, FMLP caused a greater increase in PVR. PMN depletion with dimethylmyleran significantly reduced the PVR response to FMLP. Pretreatment with two dissimilar cyclooxygenase inhibitors, meclofenamate and ibuprofen, and the leukotriene synthesis blocker MK 886 had no effect on the FMLP-induced vasoconstriction. However, the reactive oxygen species scavenger catalase significantly reduced the vasoconstriction. These results suggest that FMLP induces vasoconstriction that is dependent on PMNs and mediated by reactive oxygen species with no involvement of cyclooxygenase or lipoxygenase products.
Tanaka
H
H
Department of Anesthesiology, St. Louis University School of Medicine, Missouri 63110.
Bradley
J D
JD
Baudendistel
L J
LJ
Dahms
T E
TE
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005609:Free Radicals; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D005609:Free Radicals; D015289:Leukotrienes; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002374:Catalase; D010100:Oxygen