Leukotriene C4 affects pulmonary and cardiovascular dynamics in monkey

Smedegård, G.; Hedqvist, Per; Dahlén, Sven‐Erik; Revenäs, Björn; Hammarström, Sven; Samuelsson, Bengt

doi:10.1038/295327a0

Cited by 188 publications

(50 citation statements)

References 14 publications

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“…This effect has been shown to exist in platelets where aspirin decreased cyclooxygenase products while simultaneously increasing lipoxygenase products (28). If this phenomenon occurred in our system, the aforementioned residual pressor response seen in the presence of cyclooxygenase inhibitors may have been caused by a vasoconstricting lipoxygenase product (29). Additional factors that might account for the lack of a strict correlation between thromboxane levels and the degree of vasoconstriction are variabilities in (a) the reactivity of pulmonary vascular beds between rabbits, (b) the responsiveness of individual rabbits to thromboxane, prostacycin, and/or other factors, and (c) factors that affect the binding of thromboxane to its receptor.…”

Section: Resultsmentioning

confidence: 99%

Oxygen metabolites stimulate thromboxane production and vasoconstriction in isolated saline-perfused rabbit lungs.

Tate¹,

Morris²,

Schroeder³

et al. 1984

J. Clin. Invest.

207

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Abstract. Generation of reactive oxygen metabolites, thromboxane increases, and vasoconstriction have been implicated in the pathogenesis of acute edematous lung injury, such as that seen in patients with the Adult Respiratory Distress Syndrome (ARDS), but their interactions are unknown. We hypothesized that reactive 02 products would stimulate arachidonic acid metabolism in lungs and that vasoactive products of arachidonate, such as the potent vasoconstrictor thromboxane A2, might then mediate 02-metabolite-induced pulmonary vasoconstriction. We found that 02 metabolites generated by injection of purine plus xanthine oxidase caused increases in mean pulmonary artery perfusion pressures (27±4 mmHg) in isolated perfused lungs. In addition, purine plus xanthine oxidase also caused 30-fold increases in perfusate levels ofthromboxane B2 (the stable metabolite ofthromboxane A2) compared with only twofold increases in 6-keto-PGFia (the stable metabolite of prostacyclin). Moreover, prior addition of catalase inhibited both vasoconstriction and the thromboxane B2 production seen in isolated lungs following injection of purine plus xanthine oxidase. Similarly, pretreatment with cyclooxygenase inhibitors, either aspirin or indomethacin, also completely blocked thromboxane generation and markedly attenuated pressor responses usually seen after purine plus xanthine oxidase (increase in mean pulmonary artery perfusion pressures, 4.4±1.5 mmHg). Furthermore, imDr. Tate is a recipient of a Clinician-Scientist Award from the American Heart Association. Address correspondence and reprint requests to Dr.Tate, Pulmonary Division, Department of Medicine, Box 4000, Denver General Hospital, Denver, CO 80204.Received for publication 6 July 1983 and in revised form 26 April 1984. idazole, a thromboxane synthetase inhibitor, also decreased 02-metabolite-induced thromboxane generation and vasoconstriction. These results suggested that thromboxane generation might participate in 02-metaboliteinduced vasoconstriction. However, since a significant correlation between thromboxane levels and the degree ofvasoconstriction could not be demonstrated, and since addition of superoxide dismutase reduced thromboxane generation but did not affect the intensity of vasoconstriction, it is possible that thromboxane is not the only vasoactive mediator in this model. We conclude that exposing lungs to 02 metabolites results in thromboxane generation and that thromboxane is a major mediator of oxidant-induced vasoconstriction.

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Section: Resultsmentioning

confidence: 99%

Oxygen metabolites stimulate thromboxane production and vasoconstriction in isolated saline-perfused rabbit lungs.

Tate¹,

Morris²,

Schroeder³

et al. 1984

J. Clin. Invest.

207

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“…LTC4 and LTD4 have been shown to enhance human PMN leukocyte adherence to synthetic surfaces in vitro (8) and to microvascular endothelium in vivo (9). To evaluate a possible functional response of DMSO-differentiated HL-60 cells to LTC4 and LTD4, the effects of the leukotrienes on the adherence of the cells to Sephadex G-25 was examined with a previously standardized technique (Table II) …”

Section: Methodsmentioning

confidence: 99%

“…The C6-sulfidopeptide leukotriene constituents of the slow-reacting substance of anaphylaxis, leukotrienes C4 (LTC4) and D4 (LTD4), lack leukocyte chemotactic activity, but enhance the adherence of PMN leukocytes to synthetic surfaces in vitro (8) and to vascular endothelium in vivo (9). Whereas the activation of PMN leukocytes by LTC4 and LTD4 is dependent in part on stimulation of the cyclooxygenation of arachidonic acid in target cells, the major biochemical prerequisites for this selective recruitment of function have not been elucidated definitively.…”

mentioning

confidence: 99%

Stimulation by leukotriene D4 of increases in the cytosolic concentration of calcium in dimethylsulfoxide-differentiated HL-60 cells.

Baud¹,

Goetzl²,

Koo³

1987

J. Clin. Invest.

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The C6-sulfidopeptide leukotrienes C4 (LTC4) and D4 (LTD4) evoked increases in the cytosolic concentration of intracellular calcium (QCa`2Ij) in dimethylsulfoxide-differentiated HL-60 cells, as assessed by the fluorescence of quin-2. The increases in 1Ca"2Ji reached a peak within 15-90 s, attained 50% of the maximum level at 1.2 nM LTD4 and 60 nM LTC4, were greater in maximal magnitude for LTD4 than LTC4, and sub-

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“…It has been suggested that leukotrienes may stimulate epithelial cells and produce an airway smooth muscle-sensitive inhibitory factor (Hay, Farmer, Raeburn, Muccitelli, Wilson & Fedan, 1987;Hisayama, Takayanagi, Nakazato & Hirano, 1988) in addition to direct actions on the smooth muscle cells (Smedegard, Hedqvist, Dahlen, Revenas, Hammarstrom & Samuelsson, 1982). On the other hand, judging from the actions of antagonists for leukotrienes (BW755C and FPL55712), leukotrienes were thought to be involved in relaxing and contracting events on contractions evoked by histamine or carbachol (Tschirhart et al 1987).…”

Section: Epithelial Regulation Of Airwa Y Musclesmentioning

confidence: 99%

Airway epithelial cells regulate membrane potential, neurotransmission and muscle tone of the dog airway smooth muscle.

Xie

Hakoda

Ito

1992

The Journal of Physiology

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SUMMARY1. The effects of epithelial cells were investigated on resting membrane potential and neuro-effector transmission in smooth muscle cells of the dog tracheal and bronchiolar tissues.2. The mean value of the resting membrane potential of the epithelium-intact bronchiolar smooth muscle cells of the dog was -700 + 1 mV (± S.D., n = 40) and mechanical denudation of the epithelial layer depolarized the membrane to -57 0 + 2'5 mV (± S.D., n = 40). Application of isolated and dispersed epithelial cells (> 2 x 105 cells/ml) to the perfusing solution repolarized the membrane of epithelium-denuded bronchiolar smooth muscle cells to -670 + 2-7 mV (± S.D., n = 20).The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59-1 + 1-4 mV (± S.D., n = 50), and application of isolated and dispersed cells (> 2 x 105 cells/ml) hyperpolarized the membrane to -67-2 + 1'8 mV (± S.D., n = 50). These repolarizing actions were not modified by indomethacin (10-5 M).3. In the epithelium-denuded bronchioles, ACh (> 10-9 M) dose-dependently depolarized the smooth muscle cells, while in the epithelium-intact bronchioles, ACh (10-11-10-8 M) did not affect the resting membrane potential. At a concentration of 10-7 M, ACh significantly depolarized the membrane.4. Electrical field stimulation (EFS; 50,ts in duration and about 10-20 V in strength) applied to ring preparations of the bronchioles evoked twitch-like contractions (hereafter referred as twitch contraction), and size of the twitch contractions gradually and continuously decreased in the presence or absence of indomethacin (10-5 M) and guanethidine (10-6 M). When similar experiments were performed using epithelium-denuded bronchiolar ring preparations, in no case was there a prominent reduction in the amplitude of the twitch contractions in the presence of indomethacin and guanethidine.5. The decremental response of the twitch contraction observed in the epitheliumintact bronchioles was overcome by application of the leukotriene synthesis inhibitor AA861 (10-6 M) and the leukotriene antagonist ON01078 (10-5 M).6. Leukotrienes C4 and D4 (LTC4 and LTD4, > 10-8 M) evoked muscle contraction with a steady increase in muscle tone, up to a certain level. However, at 10-9 M, LTC4 increased and LTD4 decreased the amplitude of the twitch contractions evoked by MS 9432

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Leukotriene C4 affects pulmonary and cardiovascular dynamics in monkey

Cited by 188 publications

References 14 publications

Oxygen metabolites stimulate thromboxane production and vasoconstriction in isolated saline-perfused rabbit lungs.

Oxygen metabolites stimulate thromboxane production and vasoconstriction in isolated saline-perfused rabbit lungs.

Stimulation by leukotriene D4 of increases in the cytosolic concentration of calcium in dimethylsulfoxide-differentiated HL-60 cells.

Airway epithelial cells regulate membrane potential, neurotransmission and muscle tone of the dog airway smooth muscle.

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