Importance of secondary TXA2 release in mediating of endothelin-1 induced bronchoconstriction and vasopressin in the guinea-pig

Lueddeckens, G; Bigl, H; Sperling, J.; Becker, K.; Braquet, P.; Förster, W

doi:10.1016/0952-3278(93)90095-e

Cited by 16 publications

(16 citation statements)

References 8 publications

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“…The bronchoconstrictor nature of ET-1 has been concluded from the global changes in the mechanical parameters of the lung [6][7][8][9][10][11]. However, the situation is confused by observations that pulmonary parenchymal tissues may also contribute to the mechanical alterations in the lung during bronchoconstriction [12][13][14], as demonstrated by recent studies involving a modelbased evaluation of pulmonary impedance (ZL) [15][16][17].…”

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confidence: 85%

“…It has previously been demonstrated that i.v. ET-1 induces dose-dependent increases in the peak pulmonary inflation pressure [8][9][10] or elevations in total lung resistance and decreases in dynamic lung compliance [6,7,11]. However, it should be stressed that these parameters are indicators only of the changes in the global lung mechanics: the peak inflation pressure, combining the resistive and elastic responses, and the total respiratory or pulmonary resistance, combining the airway and tissue properties in a frequency-dependent manner.…”

Section: Methodological Viewmentioning

confidence: 99%

“…In the airways, the ETA and ETB receptor types coexist [2,3] and both are involved in ET-1-induced bronchoconstriction [4,5]. In the guinea-pig, the ETB receptors predominate in the lung [3], and the proportion of ETB is greater in the bronchi than in the trachea [2].The bronchoconstrictor nature of ET-1 has been concluded from the global changes in the mechanical parameters of the lung [6][7][8][9][10][11]. However, the situation is confused by observations that pulmonary parenchymal tissues may also contribute to the mechanical alterations in the lung during bronchoconstriction [12][13][14], as demonstrated by recent studies involving a modelbased evaluation of pulmonary impedance (ZL) [15][16][17].…”

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confidence: 99%

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Endothelin-1-induced airway and parenchymal mechanical responses in guinea-pigs: the roles of ETA and ETB receptors

Adamicza¹,

Peták²,

Asztalos³

et al. 2001

Eur Respir J

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Endothelin-1 (ET-1) has been shown to have a constrictor effect on the airways and parenchyma; however, the roles of the ETA and ETB receptors in the ET-1-induced changes in the airway and tissue compartments have not been fully explored.Low-frequency pulmonary impedance (ZL) was measured in anaesthetized, paralysed, open-chest guinea-pigs. ZL spectra were fitted by a model to estimate airway resistance (Raw) and inertance (Iaw), and coefficients of tissue damping (G) and elastance (H), and hysteresivity (g~G/H).Two Endothelin-1 (ET-1) is a powerful regulator of smooth muscle tone in many systems in both physiological and pathophysiological conditions. ET-1 induces vasoconstrictor and bronchoconstrictor responses, which suggests that an upregulated ET-1 release may play an important role in a variety of pulmonary disorders, such as pulmonary hypertension or bronchial asthma. Vasoconstriction is mediated by the ETA receptors, whereas the ETB receptors mediate both vasoconstriction and vasodilation, depending on the species and the particular circulatory region [1]. In the airways, the ETA and ETB receptor types coexist [2,3] and both are involved in ET-1-induced bronchoconstriction [4,5]. In the guinea-pig, the ETB receptors predominate in the lung [3], and the proportion of ETB is greater in the bronchi than in the trachea [2].The bronchoconstrictor nature of ET-1 has been concluded from the global changes in the mechanical parameters of the lung [6][7][8][9][10][11]. However, the situation is confused by observations that pulmonary parenchymal tissues may also contribute to the mechanical alterations in the lung during bronchoconstriction [12][13][14], as demonstrated by recent studies involving a modelbased evaluation of pulmonary impedance (ZL) [15][16][17].In vivo evidence for ET-1-induced parenchymal changes is difficult to establish. Although Nagase et al. [5] observed that ET-1 may cause increases in airway and tissue resistance and tissue elastance in the guinea-pig lung, the contribution of the parenchyma to the net effects has not been fully elucidated. These authors measured inhomogeneous local alveolar pressures, and it has been demonstrated that such sampling may not be representative of the global state, since the regional variability of isolated mechanical alterations cannot be excluded [15]. Separate characterization of the airway and parenchymal components has recently been achieved with the ZL-assessment technique, and it has been demonstrated that increasing doses of ET-1 elicit dose-dependent increases in the airway and parenchymal parameters in guinea-pigs [17].The aim of the present study was to assess whether pretreatment with ET receptor antagonists would influence the pulmonary responses to two doses of exogenous ET-1. In a previous paper [17] it was demonstrated that increasing doses of ET-1 in the range 0.05-0.8 nmol?kg -1 induced dose-dependent elevations in the airway and parenchymal parameters in guinea-pigs. In the present study, two of these doses were chosen: the lowest...

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confidence: 85%

Section: Methodological Viewmentioning

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Endothelin-1-induced airway and parenchymal mechanical responses in guinea-pigs: the roles of ETA and ETB receptors

Adamicza¹,

Peták²,

Asztalos³

et al. 2001

Eur Respir J

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“…When ET-1 binds to its receptors, it mediates vasoconstriction by two pathways: 1) it changes intracellular calcium; and 2) it stimulates secondary release of the vasoconstrictors TxA 2 and PGF 2␣ (21). This second pathway seems to be a major mechanism in the pulmonary vasoconstriction induced by ET-1 injection (13). We have previously shown that the lung tissue expression and plasma concentration of ET-1 increase during INO in endotoxic piglets (5).…”

Section: Rebound Phenomenon After Ino Withdrawalmentioning

confidence: 99%

Cyclooxygenase inhibitor blocks rebound response after NO inhalation in an endotoxin model

Chen

Mondéjar

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Chen, Luni, Hao He, Enrique Fernandez Mondejar, and Gö ran Hedenstierna. Cyclooxygenase inhibitor blocks rebound response after NO inhalation in an endotoxin model. Am J Physiol Heart Circ Physiol 284: H290-H298, 2003; 10.1152/ajpheart.00535.2002.-This study addressed the possible role of cyclooxygenase (COX) and its products in the rebound response to inhaled nitric oxide (INO). Anesthetized, mechanically ventilated piglets were exposed to endotoxin alone, endotoxin combined with INO, or endotoxin with INO plus the COX inhibitor diclofenac (3 mg/kg iv) (n ϭ 8 piglets/ group). A control group of healthy pigs (n ϭ 6) was also studied. Measurements were made of blood gases, hemodynamic parameters, lung tissue COX expression, and plasma concentrations of thromboxane B2 (TxB2), PGF2␣, and 6-keto-PGF1␣. Endotoxin increased lung inducible COX (COX-2) expression and circulating prostanoids concentrations. Inhalation of NO during endotoxemia increased the constitutive COX (COX-1) expression, and the circulating TxB2 and PGF2␣ increased further after INO withdrawal. The combination of COX inhibitor with INO blocked all these changes and eliminated the rebound reaction to INO withdrawal, which otherwise was seen in endotoxemic piglets given INO only. We conclude that the rebound response to INO discontinuation is related to COX products. nitric oxide inhalation; prostanoids INHALED NITRIC OXIDE (INO) is a selective pulmonary vasodilator in the treatment of pulmonary hypertension. However, life-threatening hemodynamic instability, reduced oxygenation, and even death have been observed during attempts to withdraw INO (1,10,17). These phenomena are referred to as the rebound response to INO withdrawal. Stepwise reduction of the NO dose implies prolongation of the NO therapy and may still not eliminate the rebound response (10).The mechanisms responsible for the rebound response are not fully understood. NO stimulates the release of soluble guanylate cyclase from the tissues, with a consequent increase in cGMP. INO reduces the endogenous NO production as a negative feedback mechanism, and this mechanism is assumed to be related to the rebound reaction to INO withdrawal (1, 2, 9). We have previously found that the production and/or release of the vasoconstrictor peptide endothelin-1 (ET-1) and possibly of other vasoconstrictors is also related to the rebound, and this may be even more important than the downregulation of endogenous NO production by INO (5).ET-1 and some prostanoids, in particular thromboxane A 2 (TxA 2 ) and PGF 2␣ , are important vasoconstriction mediators in primary and secondary pulmonary hypertension (6,22,23). In addition, ET-1-stimulated secondary release of TxA 2 is one of the main modes of signal transduction in ET-1-induced vasoconstriction (21). PGI 2 and TxA 2 , and PGF 2␣ , are important mutually antagonistic vasodilator and vasoconstrictor products, respectively, of arachidonic acid. They are synthesized via a cyclooxygenase (COX)-dependent pathway. A PGI 2 analog has been reported to mitigate th...

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“…Numerous subsequent studies on the synthesis of ET-1 in nonvascular cell types, such as airway epithelial cells, type II pneumocytes and alveolar macrophages [2± 4], have indicated the physiological and pathophysiological importance of this peptide in the lung. It is also known that ET-1 exerts a constrictor effect on both the vascular and the bronchial smooth muscles [5±11] However, the overall effect of ET-1 on lung mechanics has not been completely characterized.Previous studies revealed dose-dependent increases in the peak pulmonary inflation pressure (PIP) [7,9,10], or elevations in the total lung resistance (RL) with a concurrent decrease in the dynamic lung compliance (Cdyn) following the i.v. injection of ET-1 into guinea-pigs [5,6,8,11].…”

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Effects of endothelin-1 on airway and parenchymal mechanics in guinea-pigs

Adamicza¹,

Peták²,

Asztalos³

et al. 1999

Eur Respir J

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The contributions of the airways and the parenchyma to the overall lung mechanical response to endothelin-1 (ET-1) have not been systematically studied. In this investigation, the ET-1 induced changes on lung mechanics in guinea-pigs were separated into airway and parenchymal components.Pulmonary impedance (ZL) data were collected between 0.5 and 21 Hz in six anaesthetized, paralysed, open-chest animals by introducing small-amplitude pseudorandom oscillations into the trachea through a wave tube. ZL was calculated before and following intravenous boluses of ET-1, with doses doubled from 0.125±2 mg . kg of body weight -1 . A model containing an airway resistance (Raw) and inertance (Iaw) and tissue damping (G) and elastance (H) was fitted to the ZL spectra in each condition. Parenchymal hysteresis (g) was calculated as G/H.After each dose, ET-1 induced significant increases in Raw (at peak response meanSEM: 424129%), G (40080%), H (9522%) and g (15633%), whereas Iaw decreased following the two highest doses (-29177%).These data suggest that the parenchymal constriction was accompanied by inhomogeneous constriction of the peripheral airways. Eur Respir J 1999; 13: 767±774. Endothelin-1 (ET-1) was originally described as a potent smooth muscle constrictor derived from vascular endothelial cells [1]. Numerous subsequent studies on the synthesis of ET-1 in nonvascular cell types, such as airway epithelial cells, type II pneumocytes and alveolar macrophages [2± 4], have indicated the physiological and pathophysiological importance of this peptide in the lung. It is also known that ET-1 exerts a constrictor effect on both the vascular and the bronchial smooth muscles [5±11] However, the overall effect of ET-1 on lung mechanics has not been completely characterized.Previous studies revealed dose-dependent increases in the peak pulmonary inflation pressure (PIP) [7,9,10], or elevations in the total lung resistance (RL) with a concurrent decrease in the dynamic lung compliance (Cdyn) following the i.v. injection of ET-1 into guinea-pigs [5,6,8,11]. The measurement of these global lung mechanical parameters, however, does not allow a separate estimation of the changes in the mechanical properties of the airways and parenchyma. Recent studies partitioning the lung responses to various constrictor agents into airway and parenchymal components established the importance of the elevated tissue resistance (Rti) accompanying bronchoconstriction [12±20]. The only study on separation of the airway and parenchymal responses to ET-1 was reported by NAGASE et al. [16], who measured local alveolar pressures (PA) through one or two alveolar capsules in guinea-pigs. It has been demonstrated, however, that PA exhibits a significant heterogeneity during constriction, which makes separations based on the measurement of PA highly accidental [12,21]. Further, recent studies involving a modelbased evaluation of lung impedance (ZL) revealed that the parameters of a model of pulmonary mechanics estimated from low-frequency ZL spectra ...

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Importance of secondary TXA2 release in mediating of endothelin-1 induced bronchoconstriction and vasopressin in the guinea-pig

Cited by 16 publications

References 8 publications

Endothelin-1-induced airway and parenchymal mechanical responses in guinea-pigs: the roles of ETA and ETB receptors

Endothelin-1-induced airway and parenchymal mechanical responses in guinea-pigs: the roles of ETA and ETB receptors

Cyclooxygenase inhibitor blocks rebound response after NO inhalation in an endotoxin model

Effects of endothelin-1 on airway and parenchymal mechanics in guinea-pigs

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