Inhaled FMLP increases microvascular permeability in the rabbit trachea

Abstract

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.

Hyperresponsiveness to inhaled but not intravenous methacholine during acute respiratory syncytial virus infection in mice

“…The amount of EBD in BALF was quantified by reading the absorbance of the samples at 620 nm using a microplate reader (Bio-Tek Instruments, VT, USA). The amount of dye was calculated by interpolation on a standard curve in the range of 1 – 10 μg/ml [ 37 ]. Measurement of epithelial permeability was performed at 7 d post infection in adult mice only (n = 8 control, 7 RSV).…”

Relationship between airway microvascular leakage, edema, and baseline airway functions

“…This result mirrors findings by Kimura et al (8), who, using bradykinin, also illustrated edema outside the airway smooth muscle in airways with a perimeter Ͼ3 mm, with approximately a fourfold increase in microvascular leakage. The method of assessment of microvascular leakage by using Evans blue concentration was based on previous experience in our laboratory (2,9), with the latter study showing microvascular leakage to be maximal at 30 min when FMLP-induced increases in airway resistance are fully reversed (3).…”

Methylprednisolone reduces airway microvascular permeability but not airway resistance induced by N‐formylmethionine leucyl‐phenylalanine in the rabbit

“…FMLP contracts human bronchial smooth muscle in vitro 2 and if administered to humans by inhalation causes bronchoconstriction 3 . In rabbits, FMLP increases airway microvascular permeability (MVP), 4 an essential component of inflammation.…”