Effects of nordihydroguaiuretic acid on sulfidopeptide leukotriene activity and hypoxic pulmonary vasoconstriction in the isolated sheep lung

Schnader, Jeff; Undem, Bradley J.; Peters, S. P.; Sylvester, J. J.

doi:10.1016/0090-6980(93)90058-f

Cited by 6 publications

(7 citation statements)

References 24 publications

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“…In contrast, more recent studies demonstrated that hypoxia did not increase leukotriene synthesis in parenchymal lung cells (1475) or isolated lungs (1232,1726,1727). Moreover, inhibition of lipoxygenase or leukotriene receptors did not inhibit HPV in lungs of dogs (590, 1124,1902), ferrets (647,1938), pigs (1062), rats (1232), and sheep (1485,1727) or hypoxic contractions in isolated pulmonary arteries of guinea pigs (1926), pigs (1282), and rats (139). These data indicate that leukotrienes neither mediate nor facilitate HPV.…”

Section: Iii)mentioning

confidence: 71%

“…Early studies appeared to support a role for leukotrienes in mediation of HPV, as hypoxia was reported to increase leukotriene synthesis in rat lungs (1320) and inhibitors of leukotriene synthesis and receptors to decrease HPV in lambs (1583,1734), pigs (1221), and rats (1319). In contrast, more recent studies demonstrated that hypoxia did not increase leukotriene synthesis in parenchymal lung cells (1475) or isolated lungs (1232,1726,1727). Moreover, inhibition of lipoxygenase or leukotriene receptors did not inhibit HPV in lungs of dogs (590, 1124,1902), ferrets (647,1938), pigs (1062), rats (1232), and sheep (1485,1727) or hypoxic contractions in isolated pulmonary arteries of guinea pigs (1926), pigs (1282), and rats (139).…”

Section: Iii)mentioning

confidence: 87%

“…Most interest has focused on 5-lipoxygenase, as the leukotrienes are important inflammatory mediators and the cysteinyl leukotrienes LTC 4 , LTD 4 , and LTE 4 are powerful vasoconstrictors. Initial conclusions that 5-lipoxygenase and cysteinyl leukotrienes mediated HPV were based on the effects of nonselective inhibitors and receptor antagonists (1319,1583,1734), and later studies did not support this possibility (139, 647,1221,1232,1727,1938,2059). It is unlikely that a lipoxygenase contributes to HPV as an O 2 sensor.…”

Section: Cytoplasmmentioning

confidence: 95%

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Hypoxic Pulmonary Vasoconstriction

Sylvester

Shimoda

Aaronson

et al. 2012

Physiological Reviews

607

621

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It has been known for more than 60 years, and suspected for over 100, that alveolar hypoxia causes pulmonary vasoconstriction by means of mechanisms local to the lung. For the last 20 years, it has been clear that the essential sensor, transduction, and effector mechanisms responsible for hypoxic pulmonary vasoconstriction (HPV) reside in the pulmonary arterial smooth muscle cell. The main focus of this review is the cellular and molecular work performed to clarify these intrinsic mechanisms and to determine how they are facilitated and inhibited by the extrinsic influences of other cells. Because the interaction of intrinsic and extrinsic mechanisms is likely to shape expression of HPV in vivo, we relate results obtained in cells to HPV in more intact preparations, such as intact and isolated lungs and isolated pulmonary vessels. Finally, we evaluate evidence regarding the contribution of HPV to the physiological and pathophysiological processes involved in the transition from fetal to neonatal life, pulmonary gas exchange, high-altitude pulmonary edema, and pulmonary hypertension. Although understanding of HPV has advanced significantly, major areas of ignorance and uncertainty await resolution.

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Section: Iii)mentioning

confidence: 71%

Section: Iii)mentioning

confidence: 87%

Section: Cytoplasmmentioning

confidence: 95%

See 1 more Smart Citation

Hypoxic Pulmonary Vasoconstriction

Sylvester

Shimoda

Aaronson

et al. 2012

Physiological Reviews

607

621

View full text Add to dashboard Cite

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“…30,31 We detected increased levels of cysLTs and LTB 4 in BAL fluid obtained from endotoxin-challenged wild-type mice. These results are consistent with previous reports describing increased LT levels in the BAL fluid of patients with ARDS and experimental animals with endotoxemia.…”

Section: Discussionmentioning

confidence: 94%

Attenuation of Hypoxic Pulmonary Vasoconstriction by Endotoxemia Requires 5-Lipoxygenase in Mice

Ichinose

Zapol

Sapirstein

et al. 2001

Circulation Research

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Abstract-Sepsis and endotoxemia impair hypoxic pulmonary vasoconstriction (HPV), thereby reducing systemic oxygenation. To assess the role of leukotrienes (LTs) in the attenuation of HPV during endotoxemia, the increase in left lung pulmonary vascular resistance (LPVR) before and during left mainstem bronchus occlusion (LMBO) was measured in mice with and without a deletion of the gene encoding 5-lipoxygenase (5-LO). LMBO increased the LPVR equally in saline-challenged wild-type and 5-LO-deficient mice (96Ϯ20% and 94Ϯ19%, respectively). Twenty-two hours after challenge with Escherichia coli endotoxin, the ability of LMBO to increase LPVR was markedly impaired in wild-type mice (27Ϯ7%; PϽ0.05) but not in 5-LO-deficient mice (72Ϯ9%) or in wild-type mice pretreated with MK886, an inhibitor of 5-LO activity (76Ϯ10%). Compared with wild-type mice, endotoxin-induced disruption of lung structures and inflammatory cell influx in the lung were markedly attenuated in 5-LO-deficient mice. Administration of MK571, a selective cysteinyl LT 1 receptor antagonist, 1 hour before endotoxin challenge preserved HPV and attenuated pulmonary injury in wild-type mice but did not prevent the endotoxin-induced increase in pulmonary myeloperoxidase activity. Taken together, these findings demonstrate that a 5-LO product, most likely a cysteinyl LT, contributes to the attenuation of HPV and to pulmonary injury after challenge with endotoxin. (Circ Res. 2001;88:832-838.)Key Words: cysteinyl leukotrienes Ⅲ pulmonary injury Ⅲ left mainstem bronchus occlusion H ypoxic pulmonary vasoconstriction (HPV) is characterized by vasoconstriction of pulmonary vessels in poorly ventilated hypoxic lung regions, thus optimizing pulmonary gas exchange. The sensor and effector mechanisms responsible for HPV reside in vascular smooth muscle cells of pulmonary arterioles 1,2 ; however, the precise mechanisms that mediate HPV remain incompletely understood. 3 HPV is markedly impaired in patients with clinical sepsis or the acute respiratory distress syndrome (ARDS). 4,5 Experimental endotoxemia has also been shown to impair HPV in several animal species. 6,7 Although the mechanisms responsible for the sepsis-induced attenuation of HPV remain incompletely elucidated, various inflammatory mediators including prostaglandins, 8 thromboxanes, 9 platelet-activating factor, 6 and cytokines 10 have all been implicated. Recently, we reported that increased pulmonary NO levels are necessary, but not sufficient, to impair HPV in a murine sepsis model. 11 These studies suggested that, in addition to increased pulmonary NO levels, the attenuation of HPV after endotoxin challenge requires unknown endotoxin-induced inflammatory products.Leukotrienes (LTs) are potent lipid mediators of inflammation derived from arachidonic acid (AA) metabolism. 12 Synthesis of LTs is initiated by the conversion of AA to HPETE by arachidonate 5-lipoxygenase (5-LO) in the presence of 5-LO-activating protein (FLAP). This intermediate can be dehydrated to the epoxide intermediate LTA 4 , which c...

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“…In addition to excluding the effects of other organs and their systems, the extent of perfusion and ventilation can be controlled separately in a V/P lung. Because of these advantages, many studies have been performed using the V/P lung method in various species such as sheep, pigs, canines, rabbits, rats, and even mice 7, 9, 10, 11, 12, 13, 14, 15, 16Fig.…”

Section: Experimental Methods For Studying Hpvmentioning

confidence: 99%

Integrative understanding of hypoxic pulmonary vasoconstriction using in vitro models: from ventilated/perfused lung to single arterial myocyte

Yoo

Park

Kim

et al. 2014

Integrative Medicine Research

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Contractile response of a pulmonary artery (PA) to hypoxia (hypoxic pulmonary vasoconstriction; HPV) is a unique physiological reaction. HPV is beneficial for the optimal distribution of blood flow to differentially ventilated alveolar regions in the lung, thereby preventing systemic hypoxemia. Numerous in vitro studies have been conducted to elucidate the mechanisms underlying HPV. These studies indicate that PA smooth muscle cells (PASMCs) sense lowers the oxygen partial pressure (PO2) and contract under hypoxia. As for the PO2-sensing molecules, a variety of ion channels in PASMCs had been suggested. Nonetheless, the modulator(s) of the ion channels alone cannot mimic HPV in the experiments using PA segments and/or isolated organs. We compared the hypoxic responses of PASMCs, PAs, lung slices, and total lungs using a variety of methods (e.g., patch-clamp technique, isometric contraction measurement, video analysis of precision-cut lung slices, and PA pressure measurement in ventilated/perfused lungs). In this review, the relevant results are compared to provide a comprehensive understanding of HPV. Integration of the influences from surrounding tissues including blood cells as well as the hypoxic regulation of ion channels in PASMCs are indispensable for insights into HPV and other related clinical conditions.

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Effects of nordihydroguaiuretic acid on sulfidopeptide leukotriene activity and hypoxic pulmonary vasoconstriction in the isolated sheep lung

Cited by 6 publications

References 24 publications

Hypoxic Pulmonary Vasoconstriction

Hypoxic Pulmonary Vasoconstriction

Attenuation of Hypoxic Pulmonary Vasoconstriction by Endotoxemia Requires 5-Lipoxygenase in Mice

Integrative understanding of hypoxic pulmonary vasoconstriction using in vitro models: from ventilated/perfused lung to single arterial myocyte

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