Airway hypocapnia increases microvascular leakage in the guinea pig trachea.
We have previously shown that airway hypocapnia induced bronchoconstriction in the guinea pig lung by releasing tachykinins. To examine whether airway hypocapnia could also cause an increase in airway microvascular leakage, a tracheal segment was isolated in vivo in anesthetized guinea pigs and unidirectionally ventilated (200 ml/min) for 1 h with fully conditioned air (0% CO2) or isocapnic gas (5% CO2). The lungs were ventilated through a distally placed tracheal cannula. Microvascular leakage was quantitated by the injection of Evans blue (EB) and its extraction from the tracheal segment. EB extravasation was increased in tracheae exposed to 0% CO2 (52.3 +/- 2.0 micrograms/g wet tissue) compared with tracheae exposed to 5% CO2 (26.4 +/- 2.9 micrograms/g; p less than 0.05) and to tracheae from spontaneously breathing guinea pigs (25.2 +/- 2.3 micrograms/g; p less than 0.05). Groups of animals in which trachea were unidirectionally ventilated with 0% CO2 were then pretreated with a range of drugs in an attempt to determine the mediators responsible for the microvascular leakage with 0% CO2. Capsaicin and morphine pretreatment did not significantly alter 0% CO2-induced EB extravasation, and phosphoramidon prevented rather than increased extravasation, suggesting that tachykinins did not play a role. The hypocapnia-induced increase in microvascular leakage was, however, prevented by indomethacin pretreatment and significantly attenuated by dazmegrel, a thromboxane synthetase inhibitor. We conclude that airway hypocapnia causes microvascular leakage in the guinea pig trachea and that this effect is mediated by prostaglandins and/or thromboxane.
Reynolds
A M
AM
Department of Thoracic Medicine, Royal Adelaide Hospital, South Australia.
Zadow
S P
SP
Scicchitano
R
R
McEvoy
R D
RD
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002245:Carbon Dioxide / Q000502:physiology*; D005070:Evans Blue; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D015320:Tachykinins / Q000502:physiology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014132:Trachea / Q000098:blood supply* / Q000502:physiology
D006020:Glycopeptides; D007093:Imidazoles; D015320:Tachykinins; D002245:Carbon Dioxide; C039242:dazmegrel; D005070:Evans Blue; D009020:Morphine; D013930:Thromboxane-A Synthase; D002211:Capsaicin; C008890:phosphoramidon; D007213:Indomethacin