Summary
Pulmonary vascular responses to leukotriene (LT) D4 were compared in the sheep and cat under conditions of controlled lobar blood flow. Intralobar injections of LTD4 in the sheep caused dose-dependent increases in lobar arterial and small vein pressures without influencing left atrial or systemic arterial pressure. Leukotriene D4 was very potent in increasing pulmonary vascular resistance in the sheep, with activity similar to U-46619, a thromboxane (Tx) A2 mimic. Pulmonary vascular responses to LTD4 in the sheep were similar when the lung was ventilated and when lobar ventilation was arrested and when the lobe was perfused with blood or with dextran. Pulmonary vasoconstrictor responses to LTD4 but not to U-46619 in the sheep were reduced by inhibitors of cyclooxygenase and thromboxane synthesis. In contrast, LTD4 had modest pressor activity in the pulmonary vascular bed of the cat, whereas U-46619 had marked activity in this species. Responses to LTD4 in the cat were not altered by cyclooxygenase inhibitors.
It is concluded that LTD4 has marked pulmonary vasoconstrictor activity in the sheep, increasing pulmonary vascular resistance by constricting intrapulmonary veins and upstream segments. In this species, responses to LTD4 were independent of changes in ventilation or the interaction with formed elements but were dependent on the formation of cyclooxygenase products including TxA2. However, in the cat, LTD2 had very weak pressor activity, and this activity was not dependent on the integrity of the cyclooxygenase system. These studies indicate that there is considerable species difference in responses to LTD4, a major component of the slow reacting substance of anaphylaxis, in the pulmonary vascular bed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Borgeat, P., and Samuelsson, B., 1979a, Arachidonic acid metabolism in polymorphonuclear leukocytes: Unstable intermediates in formation of dihydroxy acids, Proc. Natl. Acad. Sci. U.S.A. 76:3212–3217.
Borgeat, P., and Samuelsson, B., 1979b, Metabolism of arachidonic acid in polymorphonuclear leukocytes: Structural analysis of novel hydroxylated compounds, J. Biol. Chem. 254:7865–7869.
Borgeat, P., Hamberg, M., and Samuelsson, B., 1976, Transformation of arachidonic acid and homo-7-linolenic acid by rabbit polymorphonuclear leukocytes. Monohydroxy acids from novel lipox-ygenases, J. Biol. Chem. 251:7816–7820.
Brocklehurst, W.E., 1960, The release of histamine and formation of a slow-reacting substance during anaphylactic shock, J. Physiol. (Lond.) 151:416–435.
Coleman, R.A., Humphrey, P.P A., Kennedy, I., Levy, G.P., and Lumley, P., 1981, Comparison of the actions of U-46619, a prostaglandin H2-analogue, with those of prostaglandin H2 and thromboxane A2 on some isolated smooth muscle preparations, Br. J. Pharmacol. 73:773–778.
Dahlen, S.E., Hedqvist, P., Hammarström, S., and Samuelsson, B., 1980, Leukotrienes are potent constrictors of human bronchi, Nature 288:484–486.
Dahlen, S.E., Hansson, G., Hedqvist, P., Bjorck, T., Granstrom, E., and Dahlen, B., 1983, Allergic challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotriene C4, D4 and E4, Proc. Natl. Acad. Sci. U.S.A. 80:1712–1716.
Drazen, J.M., Austen, K.F., Lewis, R.A., Clark, D.A., Goto, G., Marfat, A., and Corey, E.J., 1980, Comparative airway and vascular activities of leukotrienes C-1 and D in vivoand in vitro,Proc. Natl. Acad. Sci. U.S.A. 77:4354–358.
Engineer, D.M., Morris, H.R., Piper, P.J., and Sirois, P., 1978, The release of prostaglandins and thromboxanes from guinea-pig lung by slow-reacting substances of anaphylaxis and its inhibition, Br. J. Pharmacol. 64:211–218.
Ford-Hutchinson, A.W., Bray, M.A., Doig, M.V., Shipley, M.E., and Smith, M.J.H., 1980, Leukotriene B: A potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes, Nature 286:264–265.
Hammarström, S., 1983, Leukotrienes, Annu. Rev. Biochem. 52:355–377.
Hand, J.M., Will, J.A., and Buckner, C.K., 1981, Effects of leukotrienes on isolated guinea-pig pulmonary arteries, Eur. J. Pharmacol. 76:439–443.
Holroyde, M.D., Altounyan, R.E.C, Cole, M., Dixon, M., and Elliot, E.V., 1981, Bronchocon-striction produced in man by leukotrienes C and D, Lancet 2:17–18.
Hyman, A.L., and Kadowitz, P.J., 1975, Effect of alveolar and perfusion hypoxia and hypercapnia on pulmonary vascular resistance in the lamb, Am. J. Physiol. 228:397–403.
Hyman, A.L., and Kadowitz, P.J., 1979, Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat, Circ. Res. 45:404–409.
Hyman, A.L., Mathe, A.A., Leslie, C.A., Matthews, C.C, Bennett, J.T., Spannhake, E.W., and Kadowitz, P.J., 1978, Modification of pulmonary vascular responses to arachidonic acid by alterations in physiologic state, J. Pharmacol. Exp. Ther. 207:388–401.
Hyman, A. L., Spannhake, E. W., and Kadowitz, P. J., 1980, Divergent responses to arachidonic acid in the feline pulmonary vascular bed, Am. J. Physiol. 239:H40–H46.
Iacopino, V.J., Fitzpatrick, T.M., Ramwell, P.W., Rose, J.C, and Kot, P.A., 1983, Cardiovascular responses to leukotriene C4 in the rat, J. Pharmacol. Exp. Ther. 227:244–247.
Jones, T.R., Davis, C, and Daniel, E.E., 1982, Pharmacological study of the contractile activity of leukotrienes C4 and D4 on isolated human airway smooth muscle, Can. J. Physiol. Pharmacol. 60:638–643.
Kadowitz, P.J., and Hyman, A.L., 1977, Influence of a prostaglandin endoperoxide analogue on the canine pulmonary vascular bed, Circ. Res. 40:282–287.
Kadowitz, P.J., and Hyman, A.L., 1980, Comparative effects of thromboxane B2 on the canine and feline pulmonary vascular bed, J. Pharmacol. Exp. Ther. 213:300–305.
Kadowitz, P. J., and Hyman, A. L., 1983, Pulmonary vascular responses to histamine in sheep, Am. J. Physiol. 244:H423–H428.
Kadowitz, P.J., and Hyman, A.L., 1984, Analysis of responses to leukotriene D4 in the pulmonary vascular bed, Circ. Res. 55:707–717.
Kadowitz, P.J., Joiner, P.D., and Hyman, A.L., 1974, Influence of prostaglandins E1 and F2α on pulmonary vascular resistance in the sheep, Proc. Soc. Exp. Biol. Med. 145:1258–1261.
Kallaway, C.H., and Trethewie, E.F., 1940, The liberation of slow reacting smooth muscle-stimulating substances in anaphylaxis, Q. J. Exp. Physiol. 30:121–145.
Krell, R.D., Osborn, R., Vickery, L., Falcone, K., O’Donnell, M., Gleason, J., Kinzig, C, and Bryan, D., 1981, Contraction of isolated airway smooth muscle by synthetic leukotrienes C4 and D4, Prostaglandins 22:387–409.
Lewis, R.A., Austen, K.F., Drazen, J.M., Clark, D.A., Marfat, A., and Corey, E.J., 1980, Slow reacting substances of anaphylaxis: Identification of leukotrienes C and D from human and rat sources, Proc. Natl. Acad. Sci. U.S.A. 77:3710–3714.
Michelassi, F., Landa, L., Hill, R.D., Lowenstein, E., Watkins, W.D., Petkau, A.J., and Zapol, W.M., 1982, Leukotriene D4: A potent coronary artery vasoconstrictor associated with impaired ventricular contraction, Science 217:841–843.
Morris, H.R., Taylor, G.W., Piper, P.J., and Tippins, J.R., 1980, Structure of slow-reacting substance of anaphylaxis from guinea-pig lung, Nature 285:104–108.
Murphy, R.C, Hammarström, S., and Samuelsson, B., 1979, Leukotriene C: A slow reacting substance from murine mastocytoma cells, Proc. Natl. Acad. Sci. U.S.A. 76:4275–4279.
Orning, L., Hammarström, S., and Samuelsson, B., 1980, Leukotriene D: A slow reacting substance from rat basophilic leukemic cells, Proc. Natl. Acad. Sci. U.S.A. 77:2014–2017.
Piper, P.J., and Samhoum, M.N., 1981, The mechanism of action of leukotriene C4 and D4 in guinea-pig isolated perfused lung and parenchymal strips of guinea pig, Prostaglandins 21:793–803.
She, H.S., McNamara, D.B., Spannhake, E.W., Hyman, A.L., and Kadowitz, P.J., 1981, Metabolism of prostaglandin endoperoxide by microsomes from cat lung, Prostaglandins 21:531–541.
Smedegard, G., Hedqvist, P., Dahlen, S.E., Revenas, B., Hammarström, S., and Samuelsson, B., 1982, Leukotriene C4 affects pulmonary and cardiovascular dynamics in monkey, Nature 295:327–329.
Snedecor, C. W., and Cochran, W. G., 1967, Statistical Methods, 6th ed., Iowa State University Press, Ames, IA.
Spannhake, E.W., Hyman, A.L., and Kadowitz, P.J., 1980, Dependency of the airway and pulmonary vascular effects of arachidonic acid upon route and rate of administration, J. Pharmacol. Exp. Ther. 212:584–590.
Spannhake, E.W., Colombo, J.L., Craigo, P.A., McNamara, D.B., Hyman, A.L., and Kadowitz, P.J., 1983, Evidence for modification of pulmonary cyclooxygenase activity by endotoxin in the dog, J. Appl. Physiol. 54:191–198.
Weichman, B.M., Muccitelli, R.M., Osborn, R.R., Holden, D.A., Gleason, J.G., and Wasserman, M.A., 1982, In vitro and in vivo mechanisms of leukotriene-mediated bronchoconstriction in the guinea pig, J. Pharmacol. Exp. Ther. 222:202–208.
Yokochi, K., Olley, P. M., Sideris, E., Hamilton, F., Huhtanen, D., and Coceani, F., 1982, Leukotriene D4: A potent vasoconstrictor of the pulmonary and systemic circulations in the newborn lamb, in: Leukotrienes and Other Lipoxygenase Products (B. Samuelsson and R. Paoletti, eds.), Raven Press, New York, pp. 211–214.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1985 Springer Science+Business Media New York
About this chapter
Cite this chapter
Kadowitz, P.J., Mcnamara, D.B., Hyman, A.L. (1985). Comparative Responses to Leukotriene D4 in the Sheep and Cat. In: Bailey, J.M. (eds) Prostaglandins, Leukotrienes, and Lipoxins. GWUMC Department of Biochemistry Annual Spring Symposia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4946-4_28
Download citation
DOI: https://doi.org/10.1007/978-1-4684-4946-4_28
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-4948-8
Online ISBN: 978-1-4684-4946-4
eBook Packages: Springer Book Archive