The contractile action of leukotriene B₄ in the guinea‐pig lung involves a vascular component

Abstract

1 Leukotriene B 4 (LTB 4 ) is a potent leukocyte chemoattractant, acting on specific receptors, BLT receptors. The aim of this study was to examine the mechanism of action of LTB 4 in the guinea-pig lung, using strips of lung parenchyma (GPLP), spirals of trachea (GPT) and bronchus (GPB) and rings of pulmonary artery (GPPA). Mechanical responses were studied in organ baths, and mediator release was assessed using enzyme immuno assay. 2 LTB 4 induced similar contractions of GPLP and GPPA, whereas LTB 4 had only small contractile effects in GPT and GPB. In addition, the contractile response to LTB 4 was reproduced in the human pulmonary artery. 3 In the GPLP, the unselective BLT receptor antagonist ONO-4057 abolished the contractions induced by LTB 4 , whereas the selective BLT 1 receptor antagonist U-75302 only partly inhibited the LTB 4 -induced contractions. In the GPPA, both antagonists abolished the response to LTB 4 . 4 The effect of LTB 4 in GPPA and GPLP was indirect and mediated by the release of thromboxane A 2 and histamine, as supported by selective pharmacologic interventions and measurements of thromboxane B 2 and histamine in the organ baths. 5 In conclusion, the results indicate a new biological function of LTB 4 , namely to constrict isolated pulmonary arteries. Moreover, the findings suggest that the LTB 4 -induced contractions of GPPA were mediated by a BLT 1 receptor, whereas BLT 2 receptor activation accounted for a major part of the contraction of GPLP, making the latter preparation a suitable assay for BLT 2 receptors.

Leukotriene B 4 signaling through NF-κB-dependent BLT 1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia

“…4, 19, 20, and 30), was observed in human coronary artery SMC because a second addition of LTB 4 did not significantly increase whole-cell currents. The latter notion is supported further by the spontaneous reversibility of the LTB 4 -and U75302-induced currents, which is similar to results of previous pharmacological studies of BLT 1 receptors in other preparations (19,20). In sensory neurons, LTB 4 has been implicated in direct activation of ligandgated cation channels (31).…”

“…The migration of human coronary SMC toward LTB 4 was inhibited by the BLT receptor antagonists ONO 4057 and U75302. The latter compound selectively binds to BLT 1 receptors (5) and has been reported (19) to inhibit LTB 4 -induced BLT 1 receptor activation at the concentration used. At higher concentrations, U75302 is a partial agonist at the BLT 1 receptor, as shown by its stimulation of whole-cell currents and SMC proliferation in the present study.…”

“…In the latter study, it was shown that mice lacking the gene for 5-LO are protected from aortic aneurysms (18), supporting that leukotrienes may exert their effects on vascular cells producing structural elements. Also, LTB 4 is an indirectly acting vasoconstrictor in isolated guinea pig vascular preparations (19,20), and LTB 4 -induced effects on rat vascular smooth muscle cells (SMC) (21,22) have been reported, suggesting that vascular SMC may represent a target for LTB 4 in some animal models. However, the function of BLT receptors on human vascular SMC has been unknown, and the aim of the present study was to map the distribution of BLT receptors within the human vascular wall; elucidate the pharmacological and physiological responses induced by LTB 4 ; and, last, to link these responses to pathophysiological processes.…”

Saliva is one likely source of leukotriene B4in exhaled breath condensate

“…LTB 4 is produced predominantly by activated neutrophils, but also by alveolar macrophages and in transcellular reactions involving inflammatory cells and surrounding structural elements [4]. In addition to recruiting neutrophils and causing increased microvascular permeability [5], LTB 4 may stimulate lymphocyte migration in the lung [6] and constriction of pulmonary blood vessels via indirect mechanisms [7]. In comparison with healthy subjects, the LTB 4 levels have been reported to be elevated in EBC collected from subjects with asthma [8], cystic fibrosis [9] and chronic obstructive pulmonary disease (COPD) [10].…”

Mechanisms Underlying Mechanical Responses to Ephedra herb of Isolated Rabbit Urinary Bladder and Urethra, a Possible Stress Urinary Incontinence Therapeutic

“…However, receptor functions of leukotrienes in the urethra are not precisely known at this moment. It has been reported that LTB 4 , known as a potent leukocyte chemoattractant, produced contractions in the guinea-pig trachea, bronchus, and pulmonary artery and in the human pulmonary artery (25). Taken together, Ephedra herb may contract the urethra by producing several metabolites of arachidonic acid besides by stimulating α 1 -adrenoceptors.…”