Abstract
1. We studied the effects of a thromboxane A2 receptor (TP receptor) antagonist, ICI-192,605 (0.5 mg kg-1, i.v.) and a selective thromboxane (Tx) synthetase inhibitor, OKY-046 (30 mg kg-1, i.v.), on airway responses induced by leukotriene D4 (LTD4; 0.2 nmol) or prostaglandin F2 alpha (PGF2 alpha; 20 nmol) instilled via the airways route to anaesthetized guinea-pigs. For a comparison, airway responses to a TxA2-mimetic, U-46619 (0.02 nmol) were also studied. We measured both lung resistance (RL) to monitor airflow obstruction, and extravasation of Evans Blue dye to quantify airway plasma exudation. 2. Instilled LTD4 into the tracheal lumen induced an immediate peak and subsequently persistent increase in RL and produced a large amount of extravasation of Evans Blue dye at all airway levels. Both ICI-192,605 and OKY-046 significantly attenuated the persistent increase in RL following the immediate response and reduced LTD4-induced extravasation of Evans Blue dye in the trachea and proximal intrapulmonary airway. Instilled LTD4 produced significant increases in immunoreactive TxB2 in bronchoalveolar lavage fluid obtained 1.5 min after instillation of LTD4. 3. Instilled PGF2 alpha into the tracheal lumen induced an immediate increase in RL which peaked at approximately 15 s. We also observed a delayed sustained increase in RL, reaching a second peak at approximately 4 min. PGF2 alpha produced small but significant increases in the amount of Evans Blue dye at all airway levels. As with PGF2 alpha, instillation of U-46619 produced a biphasic increase in RL and extravasation of Evans Blue dye.(ABSTRACT TRUNCATED AT 250 WORDS)
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- Arakawa H., Kawikova I., Löfdahl C. G., Lötvall J. Bradykinin-induced airway responses in guinea pig: effects of inhibition of cyclooxygenase and thromboxane synthetase. Eur J Pharmacol. 1992 Dec 15;229(2-3):131–136. doi: 10.1016/0014-2999(92)90546-g. [DOI] [PubMed] [Google Scholar]
- Barnes P. J., Chung K. F., Page C. P. Inflammatory mediators and asthma. Pharmacol Rev. 1988 Mar;40(1):49–84. [PubMed] [Google Scholar]
- Beasley R. C., Featherstone R. L., Church M. K., Rafferty P., Varley J. G., Harris A., Robinson C., Holgate S. T. Effect of a thromboxane receptor antagonist on PGD2- and allergen-induced bronchoconstriction. J Appl Physiol (1985) 1989 Apr;66(4):1685–1693. doi: 10.1152/jappl.1989.66.4.1685. [DOI] [PubMed] [Google Scholar]
- Birch J., Brown E., Calnan C., Jessup C. L., Jessup R., Wayne M. Studies in the guinea-pig with ICI 185,282: a thromboxane A2 receptor antagonist. J Pharm Pharmacol. 1988 Oct;40(10):706–710. doi: 10.1111/j.2042-7158.1988.tb06999.x. [DOI] [PubMed] [Google Scholar]
- Christie P. E., Hawksworth R., Spur B. W., Lee T. H. Effect of indomethacin on leukotriene4-induced histamine hyperresponsiveness in asthmatic subjects. Am Rev Respir Dis. 1992 Dec;146(6):1506–1510. doi: 10.1164/ajrccm/146.6.1506. [DOI] [PubMed] [Google Scholar]
- Fujimura M., Sakamoto S., Nishi K., Saito M., Miyake Y., Matsuda T. Inhibitory effect of inhaled procaterol on anaphylactic bronchoconstriction and thromboxane A2 production in guinea-pigs. Clin Exp Allergy. 1991 Mar;21(2):189–194. doi: 10.1111/j.1365-2222.1991.tb00829.x. [DOI] [PubMed] [Google Scholar]
- Hadházy P., Quach Van B., Malomvölgyi B., Magyar K. Nanomolar concentrations of prostaglandin F2 alpha potentiate cholinergic contractions of rabbit isolated tracheal muscle. Eur J Pharmacol. 1982 Sep 24;83(3-4):207–212. doi: 10.1016/0014-2999(82)90253-9. [DOI] [PubMed] [Google Scholar]
- Hamel R., Masson P., Ford-Hutchinson A. W., Jones T. R., Brunet G., Piechuta H. Differing mechanisms for leukotriene d4-induced bronchoconstriction in guinea pigs following intravenous and aerosol administration. Prostaglandins. 1982 Sep;24(3):419–432. doi: 10.1016/0090-6980(82)90168-x. [DOI] [PubMed] [Google Scholar]
- Hirshman C. A., Darnell M., Brugman T., Peters J. Airway constrictor effects of leukotriene D4 in dogs with hyperreactive airways. Prostaglandins. 1983 Apr;25(4):481–490. doi: 10.1016/0090-6980(83)90020-5. [DOI] [PubMed] [Google Scholar]
- Lötvall J., Elwood W., Tokuyama K., Sakamoto T., Barnes P. J., Chung K. F. A thromboxane mimetic, U-46619, produces plasma exudation in airways of the guinea pig. J Appl Physiol (1985) 1992 Jun;72(6):2415–2419. doi: 10.1152/jappl.1992.72.6.2415. [DOI] [PubMed] [Google Scholar]
- McKenniff M. G., Norman P., Cuthbert N. J., Gardiner P. J. BAY u3405, a potent and selective thromboxane A2 receptor antagonist on airway smooth muscle in vitro. Br J Pharmacol. 1991 Nov;104(3):585–590. doi: 10.1111/j.1476-5381.1991.tb12473.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Byrne P. M., Manning P. J. Clinical relevance of lipid mediators in asthma. J Asthma. 1992;29(3):153–163. doi: 10.3109/02770909209099024. [DOI] [PubMed] [Google Scholar]
- Patel K. R. Atropine, sodium cromoglycate, and thymoxamine in PGF2 alpha-induced bronchoconstriction in extrinsic asthma. Br Med J. 1975 May 17;2(5967):360–362. doi: 10.1136/bmj.2.5967.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rogers D. F., Boschetto P., Barnes P. J. Plasma exudation. Correlation between Evans blue dye and radiolabeled albumin in guinea pig airways in vivo. J Pharmacol Methods. 1989 Jul;21(4):309–315. doi: 10.1016/0160-5402(89)90068-5. [DOI] [PubMed] [Google Scholar]
- Stenton S. C., Young C. A., Harris A., Palmer J. B., Hendrick D. J., Walters E. H. The effect of GR32191 (a thromboxane receptor antagonist) on airway responsiveness in asthma. Pulm Pharmacol. 1992 Sep;5(3):199–202. doi: 10.1016/0952-0600(92)90041-e. [DOI] [PubMed] [Google Scholar]
- Tokuyama K., Lötvall J. O., Morikawa A., Barnes P. J., Chung K. F. Role of thromboxane A2 in airway microvascular leakage induced by inhaled platelet-activating factor. J Appl Physiol (1985) 1991 Nov;71(5):1729–1734. doi: 10.1152/jappl.1991.71.5.1729. [DOI] [PubMed] [Google Scholar]
- Vincent J. E., Zijlstra F. J., Bonta I. L. The effect of inhibitors on the LTD4-induced contractions and release of thromboxane A2 in the guinea pig lung parenchymal strip. Agents Actions Suppl. 1984;14:69–81. [PubMed] [Google Scholar]
- Williams T. J. Prostaglandin E2, prostaglandin I2 and the vascular changes of inflammation. Br J Pharmacol. 1979 Mar;65(3):517–524. doi: 10.1111/j.1476-5381.1979.tb07860.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woodward D. F., Weichman B. M., Gill C. A., Wasserman M. A. The effect of synthetic leukotrienes on tracheal microvascular permeability. Prostaglandins. 1983 Jan;25(1):131–142. doi: 10.1016/0090-6980(83)90142-9. [DOI] [PubMed] [Google Scholar]