Effects of thromboxane A2 analogue on vascular resistance distribution and permeability in isolated blood-perfused dog lungs

Shibamoto, Toshishige; Wang, H. G.; Yamaguchi, Yoshihiro; Hayashi, Tetsuya; Saeki, Yuka; Tanaka, Satoshi; Koyama, Shozo

doi:10.1007/bf00181873

Cited by 13 publications

(13 citation statements)

References 27 publications

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“…The change is accompanied by an increase in pulmonary capillary pressure with progressive lung weight gain. These results suggest that pulmonary veins may play an important role in the development of pulmonary hypertension and edema when TxA 2 production increases (134).…”

Section: Constrictors Of Pulmonary Arteries and Veinsmentioning

confidence: 94%

“…In a variety of species, including the human, pulmonary veins show a greater sensitivity than arteries to a number of vasoconstrictor stimuli, such as endothelin (ET) (3,13,153,161), platelet-activating factor (PAF; 47, 111, 135), thrombox- ane (71,73,95,113,134,158,165), leukotrienes (14,102,131), and hypoxia (36,53,115,132,155,168) (Table 1). Therefore, in lung disease with hypoxia and/or increased synthesis of these vasoactive agents, venous constriction can aggravate the situation by promoting edema formation.…”

Section: Constrictors Of Pulmonary Arteries and Veinsmentioning

confidence: 99%

“…TxA 2 is a potent constrictor of pulmonary veins in a number species, including dog (71,134), sheep (73,113,165), and human (158). It causes contraction of human pulmonary veins via prostanoid receptor subtypes TP and EP 1 (158).…”

Section: Constrictors Of Pulmonary Arteries and Veinsmentioning

confidence: 99%

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Role of veins in regulation of pulmonary circulation

Gao¹,

Raj²

2005

American Journal of Physiology-Lung Cellular and Molecular Phys

104

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Pulmonary veins have been seen primarily as conduit vessels; however, over the past two decades, a large amount of evidence has accumulated to indicate that pulmonary veins can exhibit substantial vasoactivity. In this review, the role of veins in regulation of the pulmonary circulation, particularly during the perinatal period and under certain pathophysiological conditions, is discussed. In the fetus, pulmonary veins contribute a significant fraction to total pulmonary vascular resistance. At birth, the veins as well as the arteries relax in response to endothelium-derived nitric oxide and dilator prostaglandins, thereby assisting in the fall in pulmonary vascular resistance. These effects are oxygen dependent and modulated by cGMP-dependent protein kinase. Under chronic hypoxic conditions, pulmonary veins undergo remodeling and demonstrate substantial constriction and hypertrophy. In a number of species, including the human, pulmonary veins are also the primary sites of action of certain vasoconstrictors such as endothelin and thromboxane. In various pathological conditions, there is an increased synthesis of these vasoactive agents that may lead to pulmonary venous constriction, increased microvascular pressures for fluid filtration, and formation of pulmonary edema. In conclusion, the significant role of veins in regulation of the pulmonary circulation needs to be appreciated to better prevent, diagnose, and treat lung disease.

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Section: Constrictors Of Pulmonary Arteries and Veinsmentioning

confidence: 94%

Section: Constrictors Of Pulmonary Arteries and Veinsmentioning

confidence: 99%

See 1 more Smart Citation

Role of veins in regulation of pulmonary circulation

Gao¹,

Raj²

2005

American Journal of Physiology-Lung Cellular and Molecular Phys

104

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“…Because we did not detect overt evidence for hemorrhage, such as blood-stained BAL, or hemorrhagic froth in the airway, the increased lung blood content may reflect a sustained increase of lung blood volume after acid injury. Although mechanisms remain incompletely understood, acid instillation might release arachidonate metabolites, such as thromboxane A 2 , which cause lung venoconstriction (32,33), thereby increasing capillary blood volume. Hence, as proposed previously (34), the present beneficial effects of hyperosmolar sucrose may accrue partially from relief of venoconstriction.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Acid-induced Lung Injury by Hyperosmolar Sucrose in Rats

Safdar

Yiming

Grünig

et al. 2005

Am J Respir Crit Care Med

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Rationale: Acid aspiration causes acute lung injury (ALI). Recently, we showed that a brief intravascular infusion of hyperosmolar sucrose, given concurrently with airway acid instillation, effectively blocks the ensuing ALI. Objectives: The objective of the present study was to determine the extent to which intravascular infusion of hyperosmolar sucrose might protect against acid-induced ALI when given either before or after acid instillation. Methods: Our studies were conducted in anesthetized rats and in isolated, blood-perfused rat lungs. We instilled HCl through the airway, and we quantified lung injury in terms of the extravascular lung water (EVLW) content, filtration coefficient (K fc ), and cell counts and protein concentration in the bronchoalveolar lavage. We infused hyperosmolar sucrose via the femoral vein. Results: In anesthetized rats, airway HCl instillation induced ALI as indicated by a 52% increase of EVLW and a threefold increase in K fc . However, a 15-min intravenous infusion of hyperosmolar sucrose given up to 1 h before or 30 min after acid instillation markedly blunted the increases in EVLW, as well as the increases in cell count, and in protein concentration in the bronchoalveolar lavage. Hyperosmolar pretreatment also blocked the acid-induced increase of K fc . Studies in isolated perfused lungs indicated that the protective effect of hyperosmolar sucrose was leukocyte independent. Conclusions: We conclude that a brief period of vascular hyperosmolarity protects against acid-induced ALI when the infusion is administered shortly before, or shortly after, acid instillation in the airway. The potential applicability of hyperosmolar sucrose in therapy for ALI requires consideration.Keywords: acid aspiration syndrome; extravascular lung water; filtration coefficient; leukocyte count; lung blood contentThe aspiration of gastric acid, which is prone to occur in conditions such as drug overdose, stroke, and general anesthesia, is an increasingly important cause of acute lung injury (ALI), which is associated with high rates of morbidity and mortality (1). In animal models of acid-induced ALI, intratracheal acid instillation induces lung leukocyte sequestration that characteristically precedes pulmonary edema (2, 3). Accordingly, proposed therapeutic strategies include protocols that either inhibit lung leukocyte accumulation (4-8) or reduce alveolar liquid accumulation (9-11). However, strategies for lung endothelial barrier strengthening remain inadequately considered. The lung endothelial barrier, which is established by intercellular junctional proteins of endothelial cells lining lung microvessels, protects against excessive lung liquid accumulation. Decreased lung endothelial barrier function increases transmicrovascular liquid flux, thereby promoting pulmonary edema, which is a hallmark of ALI. Although it has long been known that airway acid instillation injures the lung microvascular barrier (12), relevant therapeutic strategies are not known. This article considers the possibility that...

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“…Interestingly, in vitro and ex vivo studies have indicated that thromboxane A 2 not only induces a venous constriction [29,30], but also promotes the formation of pulmonary edema [31]. Moreover, Walch et al [29] studied human pulmonary veins reporting that U46619 induces a constriction 50% higher than that of noradrenaline.…”

Section: Discussionmentioning

confidence: 99%

Endotoxin Induces Differentiated Contractile Responses in Porcine Pulmonary Arteries and Veins

et al. 2010

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Background/Aims: Sepsis-induced lung injury is characterized by pulmonary hypertension, edema and deteriorated gas exchange. As in vivo studies have indicated that bacterial endotoxin predominantly induces a pulmonary venous constriction, we aimed to investigate effects of endotoxin on isolated porcine pulmonary vessels. Methods: Pulmonary arteries and veins were examined using in vitro isometric force recordings. Endothelin-receptor protein expression and distribution were analyzed by Western blot and immunohistochemistry. Freshly isolated preparations and vessels incubated (24 h) with/without endotoxin (10 µg·ml^–1) were compared. The contractile responses to phenylephrine, UK14.304, U46619, PGF₂_α, endothelin-1 (ET-1) and sarafotoxin were recorded, as well as the relaxation in response to acetylcholine, isoproterenol and nitroprusside. Results: In freshly isolated vessels, phenylephrine-induced contractions had a 5-times larger amplitude in arteries than in veins. The amplitude of the contractions in response to sarafotoxin was nearly 2 times larger in veins than in arteries, but there was no difference in responses to ET-1. Endotoxin markedly reduced phenylephrine-induced contractions in both arteries and veins, whereas the responses to ET-1 and sarafotoxin were augmented in veins only. No apparent changes in ET receptor expression or distribution were detected with Western blot or immunohistochemistry. Conclusion: Endotoxin differentially and selectively alters the contractile responses of porcine pulmonary vessels in vitro, towards a situation where the α-1 adrenergic responses of arteries are attenuated and the ET responses of veins are augmented. In situations with high adrenergic activity and high circulating ET levels, such as sepsis, these results may provide a mechanism contributing to pulmonary hypertension and edema formation.

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Effects of thromboxane A2 analogue on vascular resistance distribution and permeability in isolated blood-perfused dog lungs

Cited by 13 publications

References 27 publications

Role of veins in regulation of pulmonary circulation

Role of veins in regulation of pulmonary circulation

Inhibition of Acid-induced Lung Injury by Hyperosmolar Sucrose in Rats

Endotoxin Induces Differentiated Contractile Responses in Porcine Pulmonary Arteries and Veins

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