Perinatal pulmonary prostaglandin production

Leffler, Charles W.; Hessler, Jack R.

doi:10.1152/ajpheart.1981.241.5.h756

Cited by 18 publications

(17 citation statements)

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“…PGI, is a potent pulmonary vasodilator in the perinatal period (3, 9, 13) and is the major PG synthesized from endogenous arachidonic acid by the perinatal pulmonary vasculature under normoxic conditions (10,11). The present study demonstrates that hypoxic pulmonary vasoconstriction is associated with an increased synthesis of PGIr from endogenous substrate in the neonatal lamb pulmonary vasculature.…”

Section: Resultsmentioning

confidence: 99%

“…The methods used are a modification of those which have been described and verified previously (8,10). Each sample was treated thusly.…”

Section: Methodsmentioning

confidence: 99%

“…The eluant was evaporated under vacuum and the invisible residue was transferred to a reaction vial for derivatization prior to analysis by gas chromatography with electron capture detection. Derivatization to pentafluorobenzyloximes of PG methyl ester trimethylsilyl ethers was accomplished as described pewiously (8,10). Analyses were performed on a Perkin-Elmer Sigma 4, equipped with heated splitless injector and h3Ni electron capture detector.…”

Section: Methodsmentioning

confidence: 99%

“…This method (8,10) is capable of quantifying as little as 5 ng of PGD2, PGE?, 6-keto-PGF,,,, TXB2, 6-keto-PGE,, or 6,15-diketo-13,14-dihydro-PGF,,, in the initial fluid sample.…”

Section: H a -'mentioning

confidence: 99%

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Hypoxia Stimulates Prostacyclin Synthesis by Neonatal Lungs

Green

Leffler

1984

Pediatr Res

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Summarysynthesis of a vasodilator PG that reduces the vasoconstriction.Inhibition of prostaglandin cyclooxygenase augments hypoxic pulmonary vasoconstriction. We used a neonatal lamb lung preparation perfused with Krebs' bicarbonate buffer to characterize and quantify prostanoids produced by the pulmonary vasculature from endogenous arachidonic acid in the absence of formed blood elements during ventilation with normoxic and hypoxic gas mixtures. Prostaglandin (PG) 12 synthesis increased from 6.4 + 2.7 ng/min (SEM) during normoxic ventilation to 14.3 f 5.4 ng/min during hypoxia and returned to 4.7 f 1.2 ng/min with resumption of normoxia. These data demonstrate that hypoxia stimulates pulmonary vascular synthesis of prostaglandin I2 from endogenous substrate in neonatal lambs and suggest that the augmentation of hypoxic pulmonary vasoconstriction by prostaglandin cyclooxygenase inhibition is due, at least in part, to interference with the synthesis of this vasodilator prostanoid. Abbreviations PG, prostanoid PG12, prostacyclin TXB2, thromboxane B2Inhibition of prostaglandin cyclooxygenase augments hypoxic pulmonary vasoconstriction in adult mammals of several species (1,12,24,27,28). A possible explanation for this observation is that hypoxia or hypoxic pulmonary vasoconstriction induces the ~nhibition of PG synthesis would remove this vasodilator PG and, thus, increase the hypoxic constriction. Indirect evidence supporting this hypothesis in the neonate includes the observations that: 1) PGIa is the most abundant PG produced by fetal bovine pulmonary arterial slices (22); 2) under normoxic conditions, PGI? is the most abundant PG produced by the newly ventilated neonatal lamb lung (10, 11); 3) PG12 is a pulmonary vasodilator in the fetal and neonatal lamb (3, 9, 13), and its vasodilatory effect on the neonatal pulmonary vasculature is more evident during hypoxic pulmonary vasoconstriction (13); and 4) hypoxic pulmonary vasoconstriction in premature and term neonatal goats is augmented by indomethacin, an inhibitor of PG synthesis (23). In the present study, we used a neonatal lamb lung preparation perfused with Krebs' bicarbonate buffer to characterize and quantify prostanoids produced by the pulmonary vasculature from endogenous arachidonic acid in the absence of formed blood elements. Pulmonary perfusate was collected during ventilation with normoxic and hypoxic gas mixtures. Analysis of these perfusates allowed determination of the effect of hypoxic pulmonary vasoconstriction on pulmonary vascular prostanoid synthesis. MATERIALS AND METHODSAnimalpreparation. Fourteen neonatal lambs [10.7 & 2.0 days old (SEM); 5.5 +. 1.6 kg) were anesthetized with 50 mg/kg achloralose IV. A tracheostomy was performed, and ventilation with room air was begun using a constant volume ventilator. A left thoracotomy was performed and the left lung was removed, leaving the mediastinum intact. Consequently, the right lung, which was to be perfused, was not exposed to the environment. The tidal volume was reduced by approximately 40%...

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Section: Resultsmentioning

confidence: 99%

“…The methods used are a modification of those which have been described and verified previously (8,10). Each sample was treated thusly.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…This method (8,10) is capable of quantifying as little as 5 ng of PGD2, PGE?, 6-keto-PGF,,,, TXB2, 6-keto-PGE,, or 6,15-diketo-13,14-dihydro-PGF,,, in the initial fluid sample.…”

Section: H a -'mentioning

confidence: 99%

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Hypoxia Stimulates Prostacyclin Synthesis by Neonatal Lungs

Green

Leffler

1984

Pediatr Res

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“…There is substantial evidence in the lamb and in other animal models that vasodilatory prostaglandins such as prostacyclin and prostaglandin E2 (PGE2) may play an integral role in these processes. The prostanoids have been implicated because: (a) they are potent dilators of the pulmonary circulation of the fetus and newborn when administered exogenously ( 10,11 ); (b) they are produced by the lungs during the transition ofthe pulmonary circulation at birth, which occurs at least in part in response to increased oxygenation ( 12,13); and (c) inhibition of prostaglandin synthesis attenuates the normal de-cline in pulmonary vascular resistance during transition ( 14,15). Pulmonary prostaglandins are primarily produced by the vascular cells, particularly the endothelium ( 16).…”

Section: Introductionmentioning

confidence: 99%

Oxygen modulates prostacyclin synthesis in ovine fetal pulmonary arteries by an effect on cyclooxygenase.

et al. 1992

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Prostacyclin (PGI2) plays an integral role in 02 mediation of pulmonary vasomotor tone in the fetus and newborn. We hypothesized that 02 modulates PG!2 synthesis in vitro in ovine fetal intrapulmonary arteries, with decreasing 02 causing attenuated synthesis. A decline in Po2 from 680 to 40 mmHg caused a 26% fall in basal PGI2 synthesis. PGI2 synthesis maximally stimulated by bradykinin, A23187, and arachidonic acid were also attenuated at low Po2, by 35%, 33%, and 35%, respectively. PGE2 synthesis was equally affected. In contrast, varying 02 did not alter PGI2 synthesis with exogenous PGH2, which is the product of cyclooxygenase and the substrate for prostacyclin synthetase. Prostaglandin-mediated effects of 02 on cAMP production were also examined. Decreasing Po2 to 40 mmHg caused complete inhibition of basal cAMP production, whereas cAMP production stimulated by exogenous PGI2 was not affected. In parallel studies of mesenteric arteries, PGI2 synthesis and cAMP production were enhanced at low 02. Thus, PGI2 synthesis in fetal intrapulmonary arteries is modulated by changes in 02, with decreasing 02 causing attenuated synthesis. This process is due to an effect on cyclooxygenase activity, it causes marked parallel alterations in cAMP production, and it is specific to the pulmonary circulation.

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