Role of venoconstriction in thromboxane-induced pulmonary hypertension and edema in lambs

Yoshimura, Kazuhiko; Tod, M.; Pier, Kristi G.; Rubin, Lewis J.

doi:10.1152/jappl.1989.66.2.929

Cited by 56 publications

(36 citation statements)

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“…TNF release cannot explain all the pathophysiologic effects previously demonstrated in neonatal piglet models of GBS sepsis ( 5 , 6). Thromboxane has been demonstrated to be a pulmonary venoconstrictor and an inducer of pulmonary edema (40). Widespread alveolar pulmonary edema would be expected to interfere with gas exchange, which was not found in these studies.…”

Section: Discussionmentioning

confidence: 65%

Tumor Necrosis Factor-Induced Neonatal Pulmonary Hypertension: Effects of Dazmegrel Pretreatment

et al. 1990

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ABSTRACT. The endogenously produced cytokine, tumor necrosis factor-a (TNF-a), has been shown in adult animal models to be associated with many of the pathophysiologic effects of sepsis, including systemic hypotension and hemorrhagic necrosis. TNF-a can induce the release of various vasoactive arachidonic acid metabolites, suggesting that TNF-a may act either directly or via intermediary substances in producing its effects. The pathophysiologic role of TNF-a in neonatal sepsis, especially its potential effect on pulmonary vascular tone, is presently unknown. To assess the role of TNF-a in neonatal sepsis, 19 piglets (19

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Section: Discussionmentioning

confidence: 65%

Tumor Necrosis Factor-Induced Neonatal Pulmonary Hypertension: Effects of Dazmegrel Pretreatment

et al. 1990

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“…3 Briefly, 23 newborn lambs of either sex, 0-4 days of age and weighing between 2.1 and 5.5 kg, were anesthetized with ketamine hydrochloride (50 mg/kg i.m. ), and a catheter was placed in a femoral artery.…”

Section: Isolated Lung Preparationmentioning

confidence: 99%

Effects of a thromboxane A2 analogue and prostacyclin on lung fluid balance in newborn lambs.

Yoshimura

Tod

Pier

et al. 1989

Circulation Research

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We have previously shown that the pulmonary venoconstriction produced by a stable thromboxane A 2 analogue (STAJ is attenuated by prostacyclin (PGIi), but PGI, increases the STA 2 -induced edema. The present study was designed to determine the effects of STA 2 and PGI 2 on the fluid balance in isolated blood-perfused newborn lamb lungs. Vascular permeability was evaluated by use of the fluid filtration coefficient (Kf) and the osmotic reflection coefficient for total proteins (cr, hematocrit-protein double indicator technique), and pulmonary capillary pressure (Pc) was estimated by the double occlusion technique. All lungs had a period of hydrostatic stress induced by elevation of the left atriai pressure from 5 to 20 mm Hg to promote fluid filtration, and the rate of lung weight gain (AW/AT) during this period was determined. Studies were made in four groups; before the hydrostatic stress, lungs were given 1) STA 2 (50 /*g, n=6), 2) PGI 2 (0.4 /ig/kg/min, n = 6), 3) both PGI 2 and STA 2 (n=6), or 4) vehicles (control, n=5). Measurements of Kf were made at the baseline period and after the hydrostatic stress. T hromboxane A 2 (TxA 2 ) is a potent pulmonary vasoconstrictor that may be involved in the early phase of endotoxin-induced pulmonary hypertension and edema. This pulmonary hypertensive response has been suggested to be the result of TxA 2 -mediated pulmonary venoconstriction since the protein-poor lung lymph flow is increased in this early phase.12 By use of the arterial and venous occlusion technique in isolated newborn lamb lungs, we have recently demonstrated that a stable TxA 2 analogue, 9,11-epithioll,12-methano-TxA 2 (STA 2 ), produced pulmonary hypertension primarily by causing pulmonary Received March 27, 1989; accepted June 16, 1989. venoconstriction. 3 Although exogenous prostacyclin (PGI 2 ) attenuated this response to STA 2 by decreasing the pulmonary venoconstriction, PGI 2 administration significantly increased the STA 2 -induced pulmonary edema.3 These observations were interpreted as being consistent with an increase in microvascular permeability by PGI 2 that potentiated the STA 2 -induced pulmonary edema, despite the attenuation of the elevation of the pulmonary microvascular pressure by PGI 2 . However, the possibility that PGI 2 increased lung vascular surface area rather than permeability was not completely excluded in this study because vascular permeability was not directly evaluated.Pulmonary microvascular membrane permeability may be estimated by changes in filtration coefficient (Kf) in isolated perfused lungs. 4 However, when changes in the number of perfused microvessels occur, as with microvascular embolism, vasodilation, or vasoconstriction, Kf may not be a reliable parameter of changes in permeability because Kf depends on membrane surface area.

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“…U-46619 (7.1 ϫ 10 Ϫ8 M) was then added to perfusate, and 15 min later Ppa, Ppv, and Pc were measured, and K f and RT were calculated. 5,37,38). This concentration has been previously shown to inhibit the release of TxA 2 , PGF 2␣ , and PGI 2 in an experimental model similar to that employed in these experiments (3,5).…”

Section: Experimental Protocolmentioning

confidence: 87%

“…In the latter two reports (37,38), the investigators, utilizing an ex vivo newborn lamb lung model, found that the K f of lungs exposed to PGI 2 and a TxA 2 -receptor agonist (9,11-epithio-11,12-methanoTxA 2 ) was significantly greater than that of lungs exposed to either PGI 2 or TxA 2 -receptor activation alone. This increase in fluid filtration was accompanied by a reduction in vascular hydrostatic pressure, suggesting that, in addition to a direct effect on microvascular permeability, PGI 2 may have increased pulmonary K f by increasing vascular surface area (37,38). These results are similar to those of the present study in that the K f of lungs exposed to PGI 2 and U-46619 was nearly 70% greater than that of lungs exposed to U-46619 alone (P Ͻ 0.02).…”

Section: Discussionmentioning

confidence: 99%

“…To the authors' knowledge, there are no studies examining the effect of PGE 2 and PGF 2␣ on TxA 2 -mediated changes in pulmonary microvascular permeability and only two studies examining the effect of PGI 2 (37,38). In the latter two reports (37,38), the investigators, utilizing an ex vivo newborn lamb lung model, found that the K f of lungs exposed to PGI 2 and a TxA 2 -receptor agonist (9,11-epithio-11,12-methanoTxA 2 ) was significantly greater than that of lungs exposed to either PGI 2 or TxA 2 -receptor activation alone.…”

Section: Discussionmentioning

confidence: 99%

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Prostaglandins potentiate U-46619-induced pulmonary microvascular dysfunction

Wright¹,

Kim²,

Rogers

et al. 2000

Journal of Applied Physiology

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.-The induction of cyclooxygenase is an important event in the pathophysiology of acute lung injury. The purpose of this study was to examine the synergistic effects of various cyclooxygenase products (PGE 2 , PGI 2 , PGF 2␣ ) on thromboxane A 2 (TxA 2 )-mediated pulmonary microvascular dysfunction. The lungs of SpragueDawley rats were perfused ex vivo with Krebs-Henseleit buffer containing indomethacin and PGE 2 (5 ϫ 10 Ϫ8 to 1 ϫ 10 Ϫ7 M), PGF 2␣ (7 ϫ 10 Ϫ9 to 5 ϫ 10 Ϫ6 M), or PGI 2 (5 ϫ 10 Ϫ8 to 2 ϫ 10 Ϫ5 M). The TxA 2 -receptor agonist U-46619 (7 ϫ 10 Ϫ8 M) was then added to the perfusate, and then the capillary filtration coefficient (K f ), pulmonary arterial pressure (Ppa), and total pulmonary vascular resistance (RT) were determined. The K f of lungs perfused with U-46619 was twice that of lungs perfused with buffer alone (P ϭ 0.05). The presence of PGE 2 , PGF 2␣ , and PGI 2 within the perfusate of lungs exposed to U-46619 caused 118, 65, and 68% increases in K f , respectively, over that of lungs perfused with U-46619 alone (P Ͻ 0.03). The RT of lungs perfused with PGE 2 ϩ U-46619 was ϳ30% greater than that of lungs exposed to either U-46619 (P Ͻ 0.02) or PGE 2 (P Ͻ 0.01) alone. When paired measurements of RT taken before and then 15 min after the addition of U-46619 were compared, PGI 2 was found to attenuate U-46619-induced increases in RT (P Ͻ 0.01). These data suggest that PGE 2 , PGI 2 , and PGF 2␣ potentiate the effects of TxA 2 -receptor activation on pulmonary microvascular permeability.capillary filtration coefficient; pulmonary vascular resistance; isolated perfused lung model THROMBOXANE A 2 (TxA 2 ) has been incriminated as an important mediator of the pulmonary microvascular dysfunction that characterizes tissue ischemia and reperfusion injury (29), endotoxin exposure (9), and cutaneous thermal injury (14). In these conditions, as well as others, TxA 2 has been shown to cause vasoconstriction and enhanced microvascular permeability. Upregulation of cyclooxygenase is an important event in the generation of TxA 2 during acute inflammatory states. Cyclooxygenase catalyzes the incorporation of molecular oxygen into arachidonic acid, yielding a cyclic endoperoxide (PGG 2 ); subsequent peroxidation yields PGH 2 , the precursor for the synthesis of TxA 2 and PGE 2 , PGI 2 , and PGF 2␣ . In general, each of these cyclooxygenase products is released by the lung in response to a particular inflammatory stimulus, albeit in varying amounts (9,14).Despite their common origin, the physiological effects of these substances on the pulmonary microvasculature are diverse. For example, TxA 2 and PGF 2␣ are constrictors of the pulmonary vasculature in rats, whereas PGI 2 is a potent vasodilator (4, 5). Furthermore, TxA 2 profoundly increases microvascular permeability, whereas the other agents have little, if any, effect by themselves (20, 27). Several investigators have reported that PGE 2 and PGI 2 potentiate the effects of histamine, bradykinin, and interleukin-1 on microvascular permeability (2,34,35). Thi...

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Role of venoconstriction in thromboxane-induced pulmonary hypertension and edema in lambs

Cited by 56 publications

References 0 publications

Tumor Necrosis Factor-Induced Neonatal Pulmonary Hypertension: Effects of Dazmegrel Pretreatment

Tumor Necrosis Factor-Induced Neonatal Pulmonary Hypertension: Effects of Dazmegrel Pretreatment

Effects of a thromboxane A2 analogue and prostacyclin on lung fluid balance in newborn lambs.

Prostaglandins potentiate U-46619-induced pulmonary microvascular dysfunction

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