Modification of hypoxic pulmonary vasoconstriction by antigen challenge in sensitized sheep

Küng, Markus; Abraham, W. M.; Greenblatt, Donald W.; Oliver, W. M.; Mingle, M.; Hughes, J. R.; Wanner, Adam

doi:10.1152/jappl.1980.49.1.22

Cited by 6 publications

(4 citation statements)

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“…The results of the present investigation suggest that in sheep with a typical hypoxic vasoconstrictor response, during hypoxia the predominant pathway is the lipoxygenase pathway, whereas in those with a blunted response, cyclooxygenase is the predominant pathway (31). Similarly, the endotoxic and allergic states might shift the arachidonic acid metabolism toward the cyclooxygenase pathway (28)(29)(30). Thus, in situations with blunted hypoxic vascular response, the mediators of prevailing cyclooxygenase pathways would mask the effects of SRS-A, and vasoconstrictor response is only observed after pretreating the animals with cyclooxygenase inhibitors.…”

Section: Discussionmentioning

confidence: 65%

“…The pattern of various mediators released from mast cells would perhaps vary, depending upon the type of challenge, i.e., hypoxic versus antigen. During antigen-induced hypoxemia, pulmonary vasoconstriction is only observed after prostaglandin synthetase inhibition (28,29), whereas during equivalent levels of exogenous hypoxia (low Fio 2 ), pulmonary vasoconstriction is observed and generally not influenced by prostaglandin synthetase inhibitors (11). This suggests that release of vasodilator prostaglandins is variable, depending upon the specific challenge to mast cells.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that release of vasodilator prostaglandins is variable, depending upon the specific challenge to mast cells. In addition to canine and ovine models of allergic asthma (28,29), prostaglandins and other products of the cyclooxygenase pathway have been implicated in the blunting of hypoxic pulmonary vasoconstriction by endotoxin infusion in dogs (30). Similarly, the hypoxic pulmonary vasoconstrictor response is naturally blunted in a minority of sheep and can be unmasked by pretreatment with indomethacin (31).…”

Section: Discussionmentioning

confidence: 99%

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Does Slow-reacting Substance of Anaphylaxis Mediate Hypoxic Pulmonary Vasoconstriction?^1–³

Ahmed¹,

Oliver

1983

Am Rev Respir Dis

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We have previously established a relationship between mast cell degranulation and hypoxic pulmonary vasoconstriction (HPV). In the present study, we investigated the possible role of slow-reacting substance of anaphylaxis (SRS-A) in the mediation of HPV. In 18 conscious sheep, pulmonary artery pressure, pulmonary arterial wedge pressure, and cardiac output were measured for the calculation of pulmonary vascular resistance (PVR) along with arterial oxygen tension (PaO2) while breathing room air and while breathing 13% O2 (balance, N2). Before and during 13% O2 breathing (pretreatment), Group 1 received an intravenous infusion of cromolyn sodium (3 mg/kg-1/min-1) and Group 2 was infused with FPL-57231, a SRS-A antagonist (2 mg/kg-1/min-1); Groups 3 and 4 received infusions of cromolyn sodium or FPL-57231 after induction of HPV. During 13% O2 breathing (mean PaO2, 47 mmHg), mean PVR increased to 190% of baseline. Pretreatment with cromolyn sodium prevented HPV, whereas infusion of cromolyn sodium after induction of HPV failed to reverse it; FPL-57231 both prevented HPV (pretreatment) and reversed it when infused after induction of HPV. Pretreatment with the prostaglandin synthetase inhibitor indomethacin (2 mg/kg) 1 h before the experiment failed to modify the FPL-57231-induced reversal of hypoxic vasoconstriction, thus excluding the release of inhibitory prostaglandins by this compound. We conclude that cromolyn sodium prevented HPV, presumably by inhibiting the release of SRS-A, which mediates pulmonary vasoconstriction directly or indirectly through other mechanisms.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Does Slow-reacting Substance of Anaphylaxis Mediate Hypoxic Pulmonary Vasoconstriction?^1–³

Ahmed¹,

Oliver

1983

Am Rev Respir Dis

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“…In both investigations, the blunted response was reversed with prostaglandin synthetase inhibitor pretreatment. Furthermore, in allergic sheep, Kung and coworkers (17) were able to reverse the pulmonary vascular response to exogenous hypoxia with subsequent antigen challenge. Those investigators concluded that during airway anaphylaxis the hypoxic pulmonary vascular response was masked by the anaphylactic release of inhibitory prostaglandins.…”

Section: Discussionmentioning

confidence: 99%

Variability of Hypoxic Pulmonary Vasoconstriction in Sheep

Ahmed

Oliver

Wanner³

1983

Am Rev Respir Dis

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In a minority of conscious sheep, the hypoxic pulmonary vasoconstrictor response is blunted ("nonresponders"). The purpose of this investigation was to determine if this blunted response is related to an increased activity of H2-histamine receptors, beta-adrenergic receptors, or the generation of inhibitory prostaglandins. We measured pulmonary arterial pressure, pulmonary arterial wedge pressure, and pulmonary blood flow for the calculation of pulmonary vascular resistance (PVR) in 5 "nonresponders" and 5 sheep with a typical hypoxic pulmonary vasoconstrictor response ("responders") while breathing room air and 13% O2 (balance, N2). Arterial oxygen tension (PaO2) was also determined as a measure of the severity of hypoxia. During hypoxia, mean PVR increased by 6% (p = NS) in the "nonresponders" (PaO2, 49 +/- 4 mmHg), and by 70% (p less than 0.01) in the "responders" (mean PaO2, 46 +/- 4 mmHg). Metiamide (H2-blocker) and propranolol (beta-adrenergic blocker) pretreatments did not restore the hypoxic pulmonary vascular response in the "nonresponders," whereas pretreatment with indomethacin (prostaglandin synthetase inhibitor) caused mean PVR to increase by 48% (p less than 0.01) during hypoxia, indicating a partial restoration of hypoxic pulmonary vasoconstriction. In the "responders," the hypoxic pulmonary vascular response was not potentiated by indomethacin pretreatment (68% increase in mean PVR). We conclude that some sheep exhibit a blunted hypoxic pulmonary vasoconstrictor response caused by enhanced production of inhibitory prostaglandins.

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Vasodilatory effect of aerosol histamine during pulmonary vasoconstriction in unanesthetized sheep

Stecenko¹,

Lefferts²,

Mitchell³

et al. 1987

Pediatric Pulmonology

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The effects of aerosol histamine on pulmonary vascular resistance during pulmonary vasoconstriction were studied in 12 unanesthetized sheep. Sheep were chronically instrumental with Silastic catheters in the pulmonary artery and left atrium, thermodilution Swan-Ganz catheter in the main pulmonary artery for measurement of cardiac output, and tracheostomy for delivery of hypoxic gas and/or aerosol histamine. Seven minutes of isocapnic hypoxia (FIO2 = 0.12) caused pulmonary artery pressure (PPA) to increase from 17.2 +/- 0.4 to 27.0 +/- 1.0 cm H2O (mean +/- SEM, P less than 0.05) and pulmonary vascular resistance (PVR) to increase from 3.94 +/- 0.33 to 4.71 +/- 0.38 cm H2O x L-1 x min (P less than 0.05). When sheep breathed a combination of aerosol histamine (5 mg/ml) and 12% O2, PPA rose only 21.3 +/- 1.11 cm H2O and PVR decreased to 3.51 +/- 0.31 cm H2O x L-1 x min. This was a significantly (P less than 0.05) smaller response compared to hypoxia alone. Aerosol histamine alone had to significant effect on PPA or PVR. Meclofenamate did not restore the histamine-induced loss of hypoxic vasoconstriction. Aerosol histamine significantly blunted the pulmonary vasoconstriction caused by intravenous serotonin (8 micrograms/kg/min) and intravenous prostaglandin H2-analog (0.74 microgram/kg/min). It was concluded that in the awake sheep aerosol histamine acted as a pulmonary vasodilator only in the presence of pulmonary vasoconstriction.

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Modification of hypoxic pulmonary vasoconstriction by antigen challenge in sensitized sheep

Cited by 6 publications

References 0 publications

Does Slow-reacting Substance of Anaphylaxis Mediate Hypoxic Pulmonary Vasoconstriction?^1–³

Does Slow-reacting Substance of Anaphylaxis Mediate Hypoxic Pulmonary Vasoconstriction?^1–³

Variability of Hypoxic Pulmonary Vasoconstriction in Sheep

Vasodilatory effect of aerosol histamine during pulmonary vasoconstriction in unanesthetized sheep

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Modification of hypoxic pulmonary vasoconstriction by antigen challenge in sensitized sheep

Cited by 6 publications

References 0 publications

Does Slow-reacting Substance of Anaphylaxis Mediate Hypoxic Pulmonary Vasoconstriction?1–3

Does Slow-reacting Substance of Anaphylaxis Mediate Hypoxic Pulmonary Vasoconstriction?1–3

Variability of Hypoxic Pulmonary Vasoconstriction in Sheep

Vasodilatory effect of aerosol histamine during pulmonary vasoconstriction in unanesthetized sheep

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Product

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Does Slow-reacting Substance of Anaphylaxis Mediate Hypoxic Pulmonary Vasoconstriction?^1–³

Does Slow-reacting Substance of Anaphylaxis Mediate Hypoxic Pulmonary Vasoconstriction?^1–³