title: Airway hypocapnia increases microvascular leakage in the guinea pig trachea.
abstract: 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.
authors.affiliation: Department of Thoracic Medicine, Royal Adelaide Hospital, South Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Reynolds
authors.forename: S P
authors.initials: SP
authors.lastname: Zadow
authors.forename: R
authors.initials: R
authors.lastname: Scicchitano
authors.forename: R D
authors.initials: RD
authors.lastname: McEvoy
mesh_terms: 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
chemical_list: 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