Leakage of macromolecules from guinea‐pig tracheobronchial microcirculation. Effects of allergen, leukotrienes, tachykinins, and anti‐asthma drugs

Abstract

The tracheobronchial mucosa of anaesthetized guinea-pigs (normal or sensitized with ovalbumin to produce IgE and IgG antibodies) was superfused (0.02 ml min-1, 5 min) with saline, mediators, and (in sensitized animals) ovalbumin via a catheter atraumatically introduced orally. The intravascular blood pool and amount of macromolecules in excised trachea and adjoining main bronchi were quantified by measuring erythrocytes, that had been labelled in vivo with 99Tcm, and analysing for FITC-dextran, MW = 70,000, that had been given i.v. Extravasation of macromolecules was determined as the analysed total content minus the calculated intravascular content of FITC-dextran. Capsaicin 0.1 nmol extravasated 223 micrograms of FITC-dextran per g wet weight of airway tissue (P less than 0.001). Substance P 0.1 nmol, 41 micrograms g-1 (P greater than 0.05); substance P 0.3 nmol, 142 micrograms g-1 (P less than 0.001); eledoisine 0.1 nmol, 101 micrograms g-1 (P less than 0.01); ovalbumin 0.1 microgram, 179 micrograms g-1 (P less than 0.001); LTC4 0.2 pmol, 180 micrograms g-1 (P less than 0.001); LTD4 0.2 pmol 223 micrograms ml-1 (P less than 0.001). Bronchi and trachea were similarly affected by these agents. Prior superfusion (0.02 ml min-1, 30 min) with terbutaline 0.06 nmol, enprofylline 12 nmol, or lidocaine 6 nmol significantly reduced the effect of capsaicin. Enprofylline also reduced significantly the effect of LTC4. The degree of extravasation in this study was smaller than could be detected by changes in tissue wet to dry weight ratios. The present data support the view that tracheobronchial vascular permeability to macromolecules is subject to physiological and pharmacological control.

Theophylline in the management of asthma: time for reappraisal?

“…Data on the effect of theophylline on plasma exudation in asthmatic airways are lacking, but the observations on some of the effects of theophylline on the late asthmatic reaction could be explained in this way. Data obtained in guinea-pig tracheobronchial mucosa demonstrate that theophylline reduces the local airways inflammatory stimulus-induced plasma exudation, although this effect may be dependent on the strength of the stimulus [103][104][105][106].…”

Bronchial Hyperreactivity in the Peripheral Airways.

“…Inflammation causes vascular dilation and increased vascular permeability with the formation of an exudate consisting of both plasma protein and migrating inflammatory cells. Antigen challenge-induced immediate asthmatic response (TAR) is reported to be associated with an increase in vascular permeability in guinea pigs (Persson et al 1986;Evans et al 1988). Cartier et al (1982) reported that allergen-induced increases in bronchial responsiveness to histamine is prolonged for as long as one month after late asthmatic response in asthmatics.…”

Mycoplasma pulmonis infections cause long-lasting potentiation of neurogenic inflammation in the respiratory tract of the rat.

“…Some ofthe rats were exposed to ammonia during this period to exacerbate the M. pulmonis infections (23)(24)(25). Thereafter, we determined the magnitude of the neurogenic inflammation evoked in the airways by a standardized dose of capsaicin, a drug known to induce neurogenic inflammation and thereby cause plasma extravasation (5,20,(26)(27)(28).…”

“…Key words: aniogenesis * capsaicin * electron microscopy -plasma extravasationpostcapillary venules * respiratory tract infections * sensory nerves * vascular permeability "Neurogenic inflammation" is a type of inflammation mediated by substances released from sensory nerves (1,2). Neurogenic inflammation in the mucosa of the respiratory tract is manifested by vasodilatation, increased vascular permeability with the extravasation of plasma proteins, diffusion ofextravasated plasma proteins into the airway lumen, adherence of leukocytes to the vascular endothelium, and secretion of mucus (3)(4)(5)(6)(7)(8).…”