Pulmonary Alveolar Hypoxia: Release of Prostaglandins and Other Humoral Mediators

Said, Sami I.; Yoshida, Tatsuyuki; Kitamura, Satoshi; Vreim, Carol E.

doi:10.1126/science.185.4157.1181

Cited by 96 publications

(29 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prostaglandins EB (PGE&)1 and F2 (PGF2a) are released from the lung by a variety of physiologic and pathophysiologic stimuli including hypoxia, anaphylaxis, hyperinflation, embolization, and pulmonary edema (6)(7)(8)(9)(10). In addition to synthesis and release the lung is a major organ for metabolism, and E and F series prostaglandins are rapidly inactivated in the lung by the enzyme prostaglandin dehydrogenase (11)(12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Effects of the 15-methyl analogs of prostaglandins E2 and F2alpha on the pulmonary circulation in the intact dog.

Kadowitz¹,

Joiner²,

Matthews³

et al. 1975

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T The effects of the 15-methyl analogs of prostaglandins E2 (PGE2) and F2. (PGF2.) on the pulmonary circulation were studied in the intact dog under conditions of controlled blood flow. Infusions of either analog into the lobar artery increased lobar arterial pressure by more than 100%. The rise in lobar arterial pressure was accompanied by a rise in lobar venous pressure and in pressure gradient from lobar artery to small vein but no change in pressure in the left atrium. The methyl analogs were about 10 times more potent than PGE2 and PGFu in elevating pulmonary vascular resistance in the dog. The effects of the analogs on the pulmonary vascular bed were similar in experiments in which the lung was perfused with dextran or with blood. Both analogs contracted isolated helical segments of canine intrapulmonary artery and vein in a dose-related manner. In other experiments the effects of passive increases in venous pressure produced by distension of a balloon catheter in the lobar vein were contrasted with the action of the analogs on the pulmonary vascular bed. Balloon distension increased pressure in the lobar artery and small vein but had no effect on pressure in the left atrium. However, in contrast to the increase in gradient with the analogs, balloon distension decreased the pressure gradient from lobar artery to small vein. Results of the present study indicate that the prostaglandin analogs increase pulmonary vascular resistance by actively constricting pulmonary veins and vessels upstream to small veins, pre-

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of the 15-methyl analogs of prostaglandins E2 and F2alpha on the pulmonary circulation in the intact dog.

Kadowitz¹,

Joiner²,

Matthews³

et al. 1975

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Wedmore and Williams (12) described increased vascular permeability in rabbit skin when chemotactic fragments were injected with prostaglandin E2, and we noted increased vascular permeability in the lung when complement activation with CVF was followed by infusion of prostaglandin E2 (13). The possible additive effect of chemotactic fragments and vasodilator prostaglandins in causing increased injury in both the skin and lung, plus the observation of Said and co-workers (14) that hypoxia leads to prostaglandin synthesis, led to the current study where hypoxia was selected as the stimulus to combine with complement activation in an attempt to produce lung injury.…”

Section: Introductionmentioning

confidence: 89%

“…One reason for selecting hypoxia as the second stimulus for challenge was the observation that hypoxia leads to generation of prostaglandins (14). Therefore, in three experiments, meclofenamate was given before and after CVF/hypoxia as described above.…”

Section: Resultsmentioning

confidence: 99%

“…First, in shock lung syndrome, a disease where complement activation with pulmonary neutrophil sequestration has been implicated in its pathogenesis (2), hypoxia and/or poor tissue oxygenation are frequently found (32,33). Second, during hypoxia, prostaglandins are generated (14), and as shown by Wedmore and Williams (12) plus Issekutz (34) in rabbit skin, and by our laboratory in rabbit lung (13), the combination of a chemotactic agent with prostaglandins can lead to an increase in albumin accumulation in the target tissue. The timing of the hypoxic challenge was designed to occur at a time known from previous observations that the pulmonary vasculature contains many neutrophils (35).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Additive effect of intravascular complement activation and brief episodes of hypoxia in producing increased permeability in the rabbit lung.

Larsen¹,

Webster²,

Worthen³

et al. 1985

J. Clin. Invest.

View full text Add to dashboard Cite

Systemic complement activation with intravascularly administered cobra venom factor (CVF) or infusion of either zymosanactivated rabbit plasma or a fifth component of complement fragment with anaphylatoxin activity in the rabbit have not caused significant increases in bronchoalveolar lavage albumin in rabbits (Webster, R. O., G. L. Larsen, B. C. Mitchell, A. J. Goins, and P. M. Henson. 1982. Am. Rev. Respir. Dis. 125:335-340). To assess if another stimulus (hypoxia) acting in concert with complement activation can produce significant lung injury, rabbits were challenged with CVF alone, 10 min of 12% oxygen alone, or CVF followed by a 10-min exposure to 12% oxygen. Either stimulus alone caused no significant changes in arterial oxygen, pulmonary resistance, or dynamic compliance during the 240 min of observation after either stimulus, and neither stimulus alone caused increased albumin accumulation in bronchoalveolar lavage over a 30-min period at the end of the experiment. However, the combination of insults significantly altered arterial oxygen, pulmonary resistance, and dynamic compliance while also increasing albumin and neutrophils recovered by lavage. The increase in lavage albumin did not appear to be due to hemodynamic events in that the pulmonary artery pressure increased acutely after CVF infusion and again during the hypoxic exposure, but was normal when albumin accumulation in the lung was measured. Neutrophil depletion with nitrogen mustard abolished all of these changes induced by CVF plus hypoxia. In addition, meclofenamate pretreatment and infusion during the 4-h study abolished the increases in lavage albumin and neutrophils as well as the increase in pulmonary artery pressure after CVF. Meclofenamate pretreatment did not, however, block accumulation of albumin in the lung (interstitium). We conclude that complement activation, as an isolated event, will not cause a significant increase in lavage albumin in this model. However, combining complement activation with an episode of hypoxia will lead to an increase in lavage albumin that is dependent on the presence of neutrophils for its expression. Meclofenamate treatment will prevent increases in lavage albumin and neutrophils while not preventing albumin accumulation in the lung

show abstract

“…Vasoactive lipids, including prostaglandins and a variety of like-acting substances, are known to be synthesized, released and metabolized in mammalian lungs during several pathophysiological conditions (Angaard & Samuelsson, 1965;Lindsey & Wyllie, 1970;Horton, Jones, Thompson & Poyser, 1971;Hamberg & Samuelsson, 1974;Said, Yoshida, Kitamura & Vreim, 1974;Dusting, Moncada & Vane, 1979). The precise role of prostaglandins in the regulation and maintenance of the pulmonary circulation is still poorly understood (Dusting et al 1979).…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Prostaglandins on Canine Intrapulmonary Arteries and Veins

Altura

Chand

1981

British J Pharmacology

View full text Add to dashboard Cite

1 The sensitivity and contractility of isolated canine intrapulmonary arteries and veins to a variety of primary prostaglandin compounds was studied.2 Intrapulmonary arteries produced no measurable contractile responses to prostaglandin A, (PGA,), PGA2, PGB,, PGD2, PGE,, PGE2 or to PGFI,. However, high concentrations of both PGB2 (> 10-7 M) and PGF2a (> 10-6 M) elicited concentrated-related, but weak, contractile responses, measuring only 5-25% of KCI-induced maximum contractions. 3 Intrapulmonary arteries, partially contracted by 5-hydroxytryptamine (5-HT), exhibited concentration-related relaxations in response to PGE,; PGE2, PGA, or PGA2 produced only weak superimposed con)actions. 4 In contrast to intrapulmonary arteries, intrapulmonary veins contracted in a concentrationrelated fashion to all prostaglandins tested, where the contractile sensitivity was (based on EC50 s and threshold concentrations): PGB2 > PGB, > PGD2 > PGF2a > PGA2 >> PGA, > PGFi, > PGE, > PGE,. 5 In terms of the ability to generate maximum contractile responses on intrapulmonary veins, the prostaglandins were also variable, with PGA2 and PGB2 being the most potent and PGD2 the least potent. 6 Intrapulmonary veins, partially contracted by 5-HT, exhibited concentration-related relaxations to PGE, at low concentrations, followed by secondary contractile responses at higher concentrations. 7 Neither PGA1 nor PGA2 (3.4 x 10-# to 3.4 x 10-5 M) inhibited or potentiated 5-HT responses of intrapulmonary arteries. 8 These data suggest that there are species, regional and major qualitative and quantitative, differences in the responsiveness of intrapulmonary arteries and veins to prostaglandin.

show abstract

Pulmonary Alveolar Hypoxia: Release of Prostaglandins and Other Humoral Mediators

Cited by 96 publications

References 15 publications

Effects of the 15-methyl analogs of prostaglandins E2 and F2alpha on the pulmonary circulation in the intact dog.

Effects of the 15-methyl analogs of prostaglandins E2 and F2alpha on the pulmonary circulation in the intact dog.

Additive effect of intravascular complement activation and brief episodes of hypoxia in producing increased permeability in the rabbit lung.

Differential Effects of Prostaglandins on Canine Intrapulmonary Arteries and Veins

Contact Info

Product

Resources

About