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A thromboxane mimetic, U-46619, produces plasma exudation in airways of the guinea pig.
J Appl Physiol (1985). 1992 Jun; 72(6):2415-9.JA

Abstract

Thromboxane A2 (TxA2) has been implicated in airway responses to allergen and in the bronchial hyperresponsiveness observed in asthma. Furthermore a TxA2 receptor antagonist and a TxA2 synthase inhibitor inhibit plasma exudation in airways induced by inhaled platelet-activating factor. To evaluate whether TxA2 has any direct effect on plasma exudation in the airways, we studied the effect of a stable TxA2 mimetic (U-46619; 2, 20, and 200 nmol/kg iv) on lung resistance (RL) and Evans blue dye extravasation (marker of plasma albumin; 20 mg/kg iv) at the airway levels of trachea, main bronchi, and proximal and distal intrapulmonary airways in anesthetized, tracheostomized, and mechanically ventilated guinea pigs. Injection of U-46619 produced an immediate and marked dose-dependent increase in RL, which peaked at approximately 30 s. At the highest dose of U-46619, we also observed a later increase in RL, starting at approximately 3 min and reaching a second peak at approximately 8 min. Mean systemic blood pressure increased in a dose-dependent manner [maximum 82 +/- 8 (SE) mmHg]. U-46619 also produces dose-dependent plasma exudation, measured as Evans blue dye extravasation, at all airway levels as well as into the tracheal lumen. Airway responses to U-46619 (200 nmol/kg iv) were abolished in animals pretreated with the TxA2 receptor antagonist ICI-192605 (0.5 mg/kg iv). We conclude that U-46619, despite being a vasoconstrictor, is potent in inducing plasma exudation in airways and that this effect is mediated via a TxA2 receptor.

Authors+Show Affiliations

Department of Thoracic Medicine, Royal Brompton National Heart and Lung Hospital, London, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1385805

Citation

Lötvall, J, et al. "A Thromboxane Mimetic, U-46619, Produces Plasma Exudation in Airways of the Guinea Pig." Journal of Applied Physiology (Bethesda, Md. : 1985), vol. 72, no. 6, 1992, pp. 2415-9.
Lötvall J, Elwood W, Tokuyama K, et al. A thromboxane mimetic, U-46619, produces plasma exudation in airways of the guinea pig. J Appl Physiol. 1992;72(6):2415-9.
Lötvall, J., Elwood, W., Tokuyama, K., Sakamoto, T., Barnes, P. J., & Chung, K. F. (1992). A thromboxane mimetic, U-46619, produces plasma exudation in airways of the guinea pig. Journal of Applied Physiology (Bethesda, Md. : 1985), 72(6), 2415-9.
Lötvall J, et al. A Thromboxane Mimetic, U-46619, Produces Plasma Exudation in Airways of the Guinea Pig. J Appl Physiol. 1992;72(6):2415-9. PubMed PMID: 1385805.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A thromboxane mimetic, U-46619, produces plasma exudation in airways of the guinea pig. AU - Lötvall,J, AU - Elwood,W, AU - Tokuyama,K, AU - Sakamoto,T, AU - Barnes,P J, AU - Chung,K F, PY - 1992/6/1/pubmed PY - 1992/6/1/medline PY - 1992/6/1/entrez SP - 2415 EP - 9 JF - Journal of applied physiology (Bethesda, Md. : 1985) JO - J. Appl. Physiol. VL - 72 IS - 6 N2 - Thromboxane A2 (TxA2) has been implicated in airway responses to allergen and in the bronchial hyperresponsiveness observed in asthma. Furthermore a TxA2 receptor antagonist and a TxA2 synthase inhibitor inhibit plasma exudation in airways induced by inhaled platelet-activating factor. To evaluate whether TxA2 has any direct effect on plasma exudation in the airways, we studied the effect of a stable TxA2 mimetic (U-46619; 2, 20, and 200 nmol/kg iv) on lung resistance (RL) and Evans blue dye extravasation (marker of plasma albumin; 20 mg/kg iv) at the airway levels of trachea, main bronchi, and proximal and distal intrapulmonary airways in anesthetized, tracheostomized, and mechanically ventilated guinea pigs. Injection of U-46619 produced an immediate and marked dose-dependent increase in RL, which peaked at approximately 30 s. At the highest dose of U-46619, we also observed a later increase in RL, starting at approximately 3 min and reaching a second peak at approximately 8 min. Mean systemic blood pressure increased in a dose-dependent manner [maximum 82 +/- 8 (SE) mmHg]. U-46619 also produces dose-dependent plasma exudation, measured as Evans blue dye extravasation, at all airway levels as well as into the tracheal lumen. Airway responses to U-46619 (200 nmol/kg iv) were abolished in animals pretreated with the TxA2 receptor antagonist ICI-192605 (0.5 mg/kg iv). We conclude that U-46619, despite being a vasoconstrictor, is potent in inducing plasma exudation in airways and that this effect is mediated via a TxA2 receptor. SN - 8750-7587 UR - https://www.unboundmedicine.com/medline/citation/1385805/A_thromboxane_mimetic_U_46619_produces_plasma_exudation_in_airways_of_the_guinea_pig_ L2 - http://www.physiology.org/doi/full/10.1152/jappl.1992.72.6.2415?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -