Direct and indirect effects of leukotriene D4 on the pulmonary and systemic circulations

T. Ahmed, B. Marchette, Adam Wanner, L. Yerger

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 μg/kg of LTD4 increased mean PVR to 421% of baseline (p < 0.001). It produced a biphasic effect on SVR that, after an initial decrease of 18% (p < 0.05), increased to 143% of baseline (p < 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 μg/kg. Dose-response curves with increasing doses of LTD4 (0.025 μg/kg to 0.5 μg/kg) revealed that the optimal dosage for maximal effect was 0.1 μg/kg. The effects of LTD4 (0.1 μg/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 < 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.

Original languageEnglish
Pages (from-to)554-558
Number of pages5
JournalAmerican Review of Respiratory Disease
Volume131
Issue number4
StatePublished - Jan 1 1985

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Leukotriene D4
Pulmonary Circulation
Vascular Resistance
Leukotriene Receptors
Vasoconstrictor Agents
Prostaglandin-Endoperoxide Synthases
Indomethacin
Pulmonary Artery
Blood Vessels
SRS-A
Hemodynamics
Lung
Injections
Cardiac Output
Sheep
Arterial Pressure

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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Direct and indirect effects of leukotriene D4 on the pulmonary and systemic circulations. / Ahmed, T.; Marchette, B.; Wanner, Adam; Yerger, L.

In: American Review of Respiratory Disease, Vol. 131, No. 4, 01.01.1985, p. 554-558.

Research output: Contribution to journalArticle

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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 μg/kg of LTD4 increased mean PVR to 421{\%} of baseline (p < 0.001). It produced a biphasic effect on SVR that, after an initial decrease of 18{\%} (p < 0.05), increased to 143{\%} of baseline (p < 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 μg/kg. Dose-response curves with increasing doses of LTD4 (0.025 μg/kg to 0.5 μg/kg) revealed that the optimal dosage for maximal effect was 0.1 μg/kg. The effects of LTD4 (0.1 μg/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 < 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.",
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