Tags

Type your tag names separated by a space and hit enter

Specificity of FPL 57231 for leukotriene D4 receptors in fetal pulmonary circulation.
Am J Physiol. 1988 Jan; 254(1 Pt 2):H120-5.AJ

Abstract

The effects of leukotriene D4 and the putative leukotriene receptor antagonist FPL 57231 were studied on the pulmonary circulation of alpha-chloralose-anesthetized fetal lambs close to term. At constant pulmonary inflow leukotriene D4 (LTD4, 0.1-10 micrograms), as bolus injections, caused dose-dependent increases in pulmonary vascular resistance. FPL 57231 (1.0-10 mg/kg) not only blocked the pressor responses to LTD4 but also lowered the normal pulmonary vascular resistance in a dose-dependent fashion. However, FPL 57231 also decreased the pulmonary pressor response to U 46619, a thromboxane A2 mimic, as well as the pressor response to phenylephrine HCl. Furthermore, the pressor responses to LTD4 were markedly reduced by cyclooxygenase inhibition. In preliminary experiments we demonstrated that the phenidone derivative, BW755C, which is a dual inhibitor of both cyclooxygenase and 5-lipoxygenase enzymes, did not block the pressor response to hypoxia. We conclude that FPL 57231 decreases fetal pulmonary vascular resistance by nonspecific mechanisms. Also the action of LTD4, is indirect and by way of the cyclooxygenase system. Although exogenous leukotrienes are able to produce a marked pulmonary pressor response, endogenous leukotrienes are probably not responsible for the hypoxic pulmonary pressor response of the fetal lung or its normally high pulmonary vascular resistance.

Authors+Show Affiliations

Department of Physiology, College of Medicine, University of Florida, Gainesville 32610.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2827522

Citation

Gause, G E., et al. "Specificity of FPL 57231 for Leukotriene D4 Receptors in Fetal Pulmonary Circulation." The American Journal of Physiology, vol. 254, no. 1 Pt 2, 1988, pp. H120-5.
Gause GE, Baker R, Cassin S. Specificity of FPL 57231 for leukotriene D4 receptors in fetal pulmonary circulation. Am J Physiol. 1988;254(1 Pt 2):H120-5.
Gause, G. E., Baker, R., & Cassin, S. (1988). Specificity of FPL 57231 for leukotriene D4 receptors in fetal pulmonary circulation. The American Journal of Physiology, 254(1 Pt 2), H120-5.
Gause GE, Baker R, Cassin S. Specificity of FPL 57231 for Leukotriene D4 Receptors in Fetal Pulmonary Circulation. Am J Physiol. 1988;254(1 Pt 2):H120-5. PubMed PMID: 2827522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Specificity of FPL 57231 for leukotriene D4 receptors in fetal pulmonary circulation. AU - Gause,G E, AU - Baker,R, AU - Cassin,S, PY - 1988/1/1/pubmed PY - 1988/1/1/medline PY - 1988/1/1/entrez SP - H120 EP - 5 JF - The American journal of physiology JO - Am J Physiol VL - 254 IS - 1 Pt 2 N2 - The effects of leukotriene D4 and the putative leukotriene receptor antagonist FPL 57231 were studied on the pulmonary circulation of alpha-chloralose-anesthetized fetal lambs close to term. At constant pulmonary inflow leukotriene D4 (LTD4, 0.1-10 micrograms), as bolus injections, caused dose-dependent increases in pulmonary vascular resistance. FPL 57231 (1.0-10 mg/kg) not only blocked the pressor responses to LTD4 but also lowered the normal pulmonary vascular resistance in a dose-dependent fashion. However, FPL 57231 also decreased the pulmonary pressor response to U 46619, a thromboxane A2 mimic, as well as the pressor response to phenylephrine HCl. Furthermore, the pressor responses to LTD4 were markedly reduced by cyclooxygenase inhibition. In preliminary experiments we demonstrated that the phenidone derivative, BW755C, which is a dual inhibitor of both cyclooxygenase and 5-lipoxygenase enzymes, did not block the pressor response to hypoxia. We conclude that FPL 57231 decreases fetal pulmonary vascular resistance by nonspecific mechanisms. Also the action of LTD4, is indirect and by way of the cyclooxygenase system. Although exogenous leukotrienes are able to produce a marked pulmonary pressor response, endogenous leukotrienes are probably not responsible for the hypoxic pulmonary pressor response of the fetal lung or its normally high pulmonary vascular resistance. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/2827522/Specificity_of_FPL_57231_for_leukotriene_D4_receptors_in_fetal_pulmonary_circulation_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.1988.254.1.H120?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -