Differential effects of leukotrienes C4, D4, and E4 in the pulmonary and systemic vasculature of sheep

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

Research output: Contribution to journalArticle

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Abstract

We investigated the comparative direct and cyclooxygenase-mediated effects of the constituents of slow-reacting substance of anaphylaxis (SRS-A), i.e., leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4) on pulmonary and systemic haemodynamics of sheep. In 20 conscious sheep, measurements of pulmonary vascular resistance (Rpv) and systemic vascular resistance (Rsv) were obtained before and after a rapid intravenous injection of LTC4 (0.1 μg.kg-1), LTD4 (0.1 μg.kg-1) and LTE4 (1 μg.kg-1). The same protocol was carried out after pretreatment with the leukotriene antagonist FPL-57231 or the cyclooxygenase inhibitor indomethacin. LTD4 increased mean Rpv to 421% of baseline (p<0.001) and had a biphasic effect on mean Rsv, which, following an initial decrease of 18% (p<0.05), increased to 143% of baseline (p<0.05). LTC4 and LTE4 had no significant efffects on Rpv, while they increased mean Rsv to 144% and 143% of baseline, respectively (p<0.05). This effect was not prreceded by a decrease in Rsv. FPL-57231 completely blocked the effects of LTC4, LTD4 and LTE4 on Rsv, and of LTD4 on Rpv. Indomethacin had no effect on LTC4, LTD4 and LTE4-induced initial increases in mean Rsv, while it prevented the LTD4-induced initial decrease in mean Rsv. Indomethacin also prevented the LTD4-induced increase in Rpv. A dose-response curve (0.05, 0.1, 0.5 and 1 μg.kg-1) demonstrated that in raising Rsv, LTE4 was approximately 10 times less potent than LTC4 and LTD4. We conclude that: a) LTC4, LTD4 and LTE4 have differential effects on pulmonary and systemic circulations of sheep, b) the effects of LTC4 and LTE4 are mediated directly by vascular leukotriene receptor stimulation, and c) LTD4 has both direct and indirect (cyclooxygenase mediated) vascular effects.

Original languageEnglish
Pages (from-to)573-580
Number of pages8
JournalClinical Respiratory Physiology
Volume22
Issue number6
StatePublished - Dec 1 1986
Externally publishedYes

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Leukotriene E4
Leukotriene D4
Leukotriene C4
Sheep
Vascular Resistance
Lung
Indomethacin
Prostaglandin-Endoperoxide Synthases
Blood Vessels
SRS-A
Leukotriene Receptors
Leukotriene Antagonists
Pulmonary Circulation
Cyclooxygenase Inhibitors
Intravenous Injections

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Differential effects of leukotrienes C4, D4, and E4 in the pulmonary and systemic vasculature of sheep. / Ahmed, T.; Marchette, B.; Wasserman, M.; Wanner, Adam; Yerger, L.

In: Clinical Respiratory Physiology, Vol. 22, No. 6, 01.12.1986, p. 573-580.

Research output: Contribution to journalArticle

Ahmed, T. ; Marchette, B. ; Wasserman, M. ; Wanner, Adam ; Yerger, L. / Differential effects of leukotrienes C4, D4, and E4 in the pulmonary and systemic vasculature of sheep. In: Clinical Respiratory Physiology. 1986 ; Vol. 22, No. 6. pp. 573-580.
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AU - Wanner, Adam

AU - Yerger, L.

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N2 - We investigated the comparative direct and cyclooxygenase-mediated effects of the constituents of slow-reacting substance of anaphylaxis (SRS-A), i.e., leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4) on pulmonary and systemic haemodynamics of sheep. In 20 conscious sheep, measurements of pulmonary vascular resistance (Rpv) and systemic vascular resistance (Rsv) were obtained before and after a rapid intravenous injection of LTC4 (0.1 μg.kg-1), LTD4 (0.1 μg.kg-1) and LTE4 (1 μg.kg-1). The same protocol was carried out after pretreatment with the leukotriene antagonist FPL-57231 or the cyclooxygenase inhibitor indomethacin. LTD4 increased mean Rpv to 421% of baseline (p<0.001) and had a biphasic effect on mean Rsv, which, following an initial decrease of 18% (p<0.05), increased to 143% of baseline (p<0.05). LTC4 and LTE4 had no significant efffects on Rpv, while they increased mean Rsv to 144% and 143% of baseline, respectively (p<0.05). This effect was not prreceded by a decrease in Rsv. FPL-57231 completely blocked the effects of LTC4, LTD4 and LTE4 on Rsv, and of LTD4 on Rpv. Indomethacin had no effect on LTC4, LTD4 and LTE4-induced initial increases in mean Rsv, while it prevented the LTD4-induced initial decrease in mean Rsv. Indomethacin also prevented the LTD4-induced increase in Rpv. A dose-response curve (0.05, 0.1, 0.5 and 1 μg.kg-1) demonstrated that in raising Rsv, LTE4 was approximately 10 times less potent than LTC4 and LTD4. We conclude that: a) LTC4, LTD4 and LTE4 have differential effects on pulmonary and systemic circulations of sheep, b) the effects of LTC4 and LTE4 are mediated directly by vascular leukotriene receptor stimulation, and c) LTD4 has both direct and indirect (cyclooxygenase mediated) vascular effects.

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