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Direct and indirect effects of leukotriene D4 on the pulmonary and systemic circulations.
Am Rev Respir Dis. 1985 Apr; 131(4):554-8.AR

Abstract

We investigated direct (vascular leukotriene receptor stimulation) and indirect (generation of cyclooxygenase metabolites) hemodynamic effects of leukotriene D4 (LTD4) in 6 conscious sheep. Pulmonary artery, pulmonary arterial wedge and systemic arterial pressures, and cardiac output were measured. From these parameters, pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) were calculated before and immediately after a rapid injection of LTD4 into the pulmonary artery. Injection of 0.1 micrograms/kg of LTD4 increased mean PVR to 421% of baseline (p less than 0.001). It produced a biphasic effect on SVR that, after an initial decrease of 18% (p less than 0.05), increased to 143% of baseline (p less than 0.05). Both PVR and SVR returned to baseline within 10 min. The same results were obtained when the dose of LTD4 was increased to 0.5 micrograms/kg. Dose-response curves with increasing doses of LTD4)0.025 micrograms/kg to 0.5 micrograms/kg) revealed that the optimal dosage for maximal effect was 0.1 micrograms/kg. The effects of LTD4 (0.1 micrograms/kg) on the pulmonary circulation were completely blocked by the SRS-A antagonist, FPL-57231, as well as by indomethacin. In the systemic circulation, FPL-57231 blocked the biphasic effects of LTD4 on SVR, whereas indomethacin prevented the initial decrease without attenuating the subsequent increase in mean SVR (135% of baseline, p less than 0.05). We conclude that there are direct and indirect hemodynamic effects of LTD4: the systemic vasoconstrictor response is directly related to vascular leukotriene receptor stimulation, whereas activation of cyclooxygenase pathway products is responsible for the pulmonary vasoconstrictor and systemic depressor responses.

Authors

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Pub Type(s)

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

Language

eng

PubMed ID

2986501

Citation

Ahmed, T, et al. "Direct and Indirect Effects of Leukotriene D4 On the Pulmonary and Systemic Circulations." The American Review of Respiratory Disease, vol. 131, no. 4, 1985, pp. 554-8.
Ahmed T, Marchette B, Wanner A, et al. Direct and indirect effects of leukotriene D4 on the pulmonary and systemic circulations. Am Rev Respir Dis. 1985;131(4):554-8.
Ahmed, T., Marchette, B., Wanner, A., & Yerger, L. (1985). Direct and indirect effects of leukotriene D4 on the pulmonary and systemic circulations. The American Review of Respiratory Disease, 131(4), 554-8.
Ahmed T, et al. Direct and Indirect Effects of Leukotriene D4 On the Pulmonary and Systemic Circulations. Am Rev Respir Dis. 1985;131(4):554-8. PubMed PMID: 2986501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Direct and indirect effects of leukotriene D4 on the pulmonary and systemic circulations. AU - Ahmed,T, AU - Marchette,B, AU - Wanner,A, AU - Yerger,L, PY - 1985/4/1/pubmed PY - 1985/4/1/medline PY - 1985/4/1/entrez SP - 554 EP - 8 JF - The American review of respiratory disease JO - Am Rev Respir Dis VL - 131 IS - 4 N2 - We investigated direct (vascular leukotriene receptor stimulation) and indirect (generation of cyclooxygenase metabolites) hemodynamic effects of leukotriene D4 (LTD4) in 6 conscious sheep. Pulmonary artery, pulmonary arterial wedge and systemic arterial pressures, and cardiac output were measured. From these parameters, pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) were calculated before and immediately after a rapid injection of LTD4 into the pulmonary artery. Injection of 0.1 micrograms/kg of LTD4 increased mean PVR to 421% of baseline (p less than 0.001). It produced a biphasic effect on SVR that, after an initial decrease of 18% (p less than 0.05), increased to 143% of baseline (p less than 0.05). Both PVR and SVR returned to baseline within 10 min. The same results were obtained when the dose of LTD4 was increased to 0.5 micrograms/kg. Dose-response curves with increasing doses of LTD4)0.025 micrograms/kg to 0.5 micrograms/kg) revealed that the optimal dosage for maximal effect was 0.1 micrograms/kg. The effects of LTD4 (0.1 micrograms/kg) on the pulmonary circulation were completely blocked by the SRS-A antagonist, FPL-57231, as well as by indomethacin. In the systemic circulation, FPL-57231 blocked the biphasic effects of LTD4 on SVR, whereas indomethacin prevented the initial decrease without attenuating the subsequent increase in mean SVR (135% of baseline, p less than 0.05). We conclude that there are direct and indirect hemodynamic effects of LTD4: the systemic vasoconstrictor response is directly related to vascular leukotriene receptor stimulation, whereas activation of cyclooxygenase pathway products is responsible for the pulmonary vasoconstrictor and systemic depressor responses. SN - 0003-0805 UR - https://www.unboundmedicine.com/medline/citation/2986501/Direct_and_indirect_effects_of_leukotriene_D4_on_the_pulmonary_and_systemic_circulations_ L2 - https://www.atsjournals.org/doi/10.1164/arrd.1985.131.4.554?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -