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Direct and indirect effects of leukotriene D4 on the lungs of unanesthetized sheep.
Respiration. 1987; 51(4):256-65.R

Abstract

The direct and indirect actions of two active components of slow-reacting substance of anaphylaxis, leukotrienes C4 (LTC4) and D4 (LTD4), were studied in chronically instrumented unanesthetized sheep. Intravenous injection of 3 micrograms of LTD4 caused immediate marked pulmonary arterial hypertension which returned to baseline in 6.5 +/- 1.0 min. Dynamic compliance of the lungs (Cdyn) and left atrial (PLA) and aortic (Paorta) blood pressure fell concomitantly with the increases in pulmonary artery pressure (PPA). PLA and Paorta then increased above baseline and heart rate deceased significantly. LTD4 caused only small increases in lung lymph flow but did increase lung lymph concentrations of thromboxane B2. Lung lymph concentrations of 6-keto-prostaglandin F1 alpha did not increase following LTD4 infusion. The increase in PPA after 3-micrograms injections of LTD4 was greater than that caused by 10-micrograms injections of prostaglandin H2-analog. Injections of 10-30 micrograms of LTC4 caused only minor increases in PPA but did cause bradycardia and delayed increases in PLA and Paorta. The cyclooxygenase inhibitors meclofenamate and ibuprofen inhibited the increases in PPA caused by LTD4 but not the later bradycardia or increases in PLA and Paorta. The thromboxane synthetase inhibitor UK-38485 attenuated the early increase in PPA and moderated the later increases in PLA and Paorta and bradycardia caused by LTD4 injection. The response of unanesthetized sheep to LTD4 is mediated, at least in part, indirectly by stimulation of the cyclooxygenase pathway of arachidonate metabolism.

Authors+Show Affiliations

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

3116626

Citation

Ogletree, M L., et al. "Direct and Indirect Effects of Leukotriene D4 On the Lungs of Unanesthetized Sheep." Respiration; International Review of Thoracic Diseases, vol. 51, no. 4, 1987, pp. 256-65.
Ogletree ML, Snapper JR, Brigham KL. Direct and indirect effects of leukotriene D4 on the lungs of unanesthetized sheep. Respiration. 1987;51(4):256-65.
Ogletree, M. L., Snapper, J. R., & Brigham, K. L. (1987). Direct and indirect effects of leukotriene D4 on the lungs of unanesthetized sheep. Respiration; International Review of Thoracic Diseases, 51(4), 256-65.
Ogletree ML, Snapper JR, Brigham KL. Direct and Indirect Effects of Leukotriene D4 On the Lungs of Unanesthetized Sheep. Respiration. 1987;51(4):256-65. PubMed PMID: 3116626.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Direct and indirect effects of leukotriene D4 on the lungs of unanesthetized sheep. AU - Ogletree,M L, AU - Snapper,J R, AU - Brigham,K L, PY - 1987/1/1/pubmed PY - 1987/1/1/medline PY - 1987/1/1/entrez SP - 256 EP - 65 JF - Respiration; international review of thoracic diseases JO - Respiration VL - 51 IS - 4 N2 - The direct and indirect actions of two active components of slow-reacting substance of anaphylaxis, leukotrienes C4 (LTC4) and D4 (LTD4), were studied in chronically instrumented unanesthetized sheep. Intravenous injection of 3 micrograms of LTD4 caused immediate marked pulmonary arterial hypertension which returned to baseline in 6.5 +/- 1.0 min. Dynamic compliance of the lungs (Cdyn) and left atrial (PLA) and aortic (Paorta) blood pressure fell concomitantly with the increases in pulmonary artery pressure (PPA). PLA and Paorta then increased above baseline and heart rate deceased significantly. LTD4 caused only small increases in lung lymph flow but did increase lung lymph concentrations of thromboxane B2. Lung lymph concentrations of 6-keto-prostaglandin F1 alpha did not increase following LTD4 infusion. The increase in PPA after 3-micrograms injections of LTD4 was greater than that caused by 10-micrograms injections of prostaglandin H2-analog. Injections of 10-30 micrograms of LTC4 caused only minor increases in PPA but did cause bradycardia and delayed increases in PLA and Paorta. The cyclooxygenase inhibitors meclofenamate and ibuprofen inhibited the increases in PPA caused by LTD4 but not the later bradycardia or increases in PLA and Paorta. The thromboxane synthetase inhibitor UK-38485 attenuated the early increase in PPA and moderated the later increases in PLA and Paorta and bradycardia caused by LTD4 injection. The response of unanesthetized sheep to LTD4 is mediated, at least in part, indirectly by stimulation of the cyclooxygenase pathway of arachidonate metabolism. SN - 0025-7931 UR - https://www.unboundmedicine.com/medline/citation/3116626/Direct_and_indirect_effects_of_leukotriene_D4_on_the_lungs_of_unanesthetized_sheep_ L2 - https://www.karger.com?DOI=10.1159/000195211 DB - PRIME DP - Unbound Medicine ER -