Inhaled FMLP increases microvascular permeability in the rabbit trachea.
This study was designed to determine the effect of inhaled N-formyl-methionyl-leucyl-phenylalanine (FMLP) on microvascular permeability in the rabbit trachea and to determine if the effect could be modified by cholinergic antagonism, neutral endopeptidase (NEP) inhibition, opioid receptor antagonism, or an opioid agonist. New Zealand White rabbits were anesthetized and pretreated intravenously with one of the following: saline, dimethyl sulfoxide (DMSO) (both controls), thiorphan, phosphoramidon (both NEP inhibitors), thiorphan and naloxone, morphine, or atropine. All rabbits were then given intravenous Evans blue before inhalation of nebulized DMSO (control) or FMLP. Extravascular tracheal Evans blue concentration was subsequently determined spectrophotometrically. FMLP caused a highly significant increase in microvascular permeability (92.6 +/- 7.1 micrograms/g of trachea, control 20.4' +/- 3.4). The effect of FMLP was significantly modified by cholinergic blockade (61.1 +/- 6.9) and by NEP inhibition (thiorphan 38.8 +/- 5.6, phosphoramidon 52.6 +/- 4.2). This effect of NEP inhibition could be reversed by concurrent treatment with the opioid receptor antagonist naloxone (95.9 +/- 34.6). Morphine had no significant effect. We concluded that FMLP increases microvascular permeability, which may in part explain the effect of FMLP on airway resistance in the rabbit. Inhibiting NEP decreases the response possibly through an effect on endogenous opioids. The response appears to be partially vagally mediated.
Bell
S C
SC
Department of Thoracic Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia.
Rynell
A C
AC
Matheson
M J
MJ
Finnimore
A J
AJ
Berend
N
N
D000280:Administration, Inhalation; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D005070:Evans Blue; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D015244:Thiorphan / Q000494:pharmacology; D014132:Trachea / Q000098:blood supply* / Q000187:drug effects
D000804:Angiotensin II; D009270:Naloxone; D005070:Evans Blue; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009020:Morphine; D001285:Atropine; D015244:Thiorphan; D015260:Neprilysin