The Onset of Breathing at Birth Stimulates Pulmonary Vascular Prostacyclin Synthesis

Leffler, Charles W.; Hessler, Jack R.; Green, Robert S.

doi:10.1203/00006450-198418100-00006

Cited by 14 publications

(18 citation statements)

References 14 publications

(17 reference statements)

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“…Although mechanisms maintaining high pulmonary vascular resistance in the fetus are uncertain, possible explanation for this high resistance include lack of an air liquid interface or ventilation, low oxygen tension (2-7), decreased vasodilators, such as prostacyclin, bradykinin or endothelium-derived nitric oxide or increased vasoconstrictors such as platelet activating factor or leukotrienes (28)(29)(30)(31)(32)(33)(34)(35)(36)(37). Endothelin has potent vasoconstrictor properties (9), but its role in the fetal lung is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Physiologic characterization of endothelin A and B receptor activity in the ovine fetal pulmonary circulation.

Ivy¹,

Kinsella²,

Abman³

1994

J. Clin. Invest.

124

110

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To determine the potential contribution of endothelin (ET) to modulation of high pulmonary vascular resistance in the normal fetus, we studied the effects of BQ 123, a selective ET-A receptor antagonist, and sarafoxotoxin S6c (SFX), a selective ET-B receptor agonist, in 31 chronically prepared late gestation fetal lambs. Brief intrapulmonary infusions of BQ 123 (0.1-1.0 mcg/min for 10 min) caused sustained increases in left pulmonary artery flow (Qp) without changing main pulmonary artery (MPA) and aortic (Ao) pressures. In contrast, BQ 123 did not change vascular resistance in a regional systemic circulation (the fetal hindlimb). To determine whether big-endothelin-1 (big-ET-1 )-induced pulmonary vasoconstriction is mediated by ET-A receptor stimulation, we studied the effects of big-ET-1 with or without pretreatment with BQ 123. BQ 123 (0.5 mcg/min for 10 min) blocked the rise in total pulmonary resistance caused by big-ET-1. CGS 27830 (100 mcg/min for 10 min), an ET-A and -B receptor antagonist, did not change basal tone but blocked big-ET-1-induced pulmonary vasoconstriction. Brief and prolonged intrapulmonary infusion of SFX (0.1 mcg/min for 10 min) increased Qp twofold without changing MPA or Ao pressures. Nitro-L-arginine (L-NA), a selective endothelium-derived nitric oxide (EDNO) antagonist, blocked vasodilation caused by BQ 123 and SFX. We conclude that: (a) BQ 123 causes sustained fetal pulmonary vasodilation, but did not change vascular resistance in the fetal hindlimb; (b) Big-ET-1-induced pulmonary vasoconstriction may be mediated through ET-A receptor stimulation; and (c) ET-B receptor stimulation causes pulmonary vasodilation through EDNO release. These findings support the hypothesis that endothelin may play a role in modulation of high basal pulmonary vascular resistance in the normal fetus. (J. Clin. Invest. 1994. 2141-2148

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Section: Discussionmentioning

confidence: 99%

Physiologic characterization of endothelin A and B receptor activity in the ovine fetal pulmonary circulation.

Ivy¹,

Kinsella²,

Abman³

1994

J. Clin. Invest.

124

110

View full text Add to dashboard Cite

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“…For example, the replacement of fluid with gas in the alveoli changes alveolar surface tension, which unkinks the small pulmonary arteries, and causes an immediate decrease in pulmonary vascular resistance and increase in pulmonary blood flow (2,5). There is also release of vasoactive substances, such as prostacyclin (PGI 2 ), which decrease pulmonary vascular resistance and increase pulmonary blood flow (6,7). Both rhythmic distension of the fetal lamb lung and ventilation without oxygenation produce partial pulmonary vasodilatation (2).…”

Section: Introductionmentioning

confidence: 99%

Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs.

Black¹,

Johengen²,

Dong³

et al. 1997

J. Clin. Invest.

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At birth, ventilation and oxygenation immediately decrease pulmonary vascular resistance (PVR) and increase pulmonary blood flow (PBF); more gradual changes occur over the next several hours. Nitric oxide, produced by endothelial nitric oxide synthase (eNOS), mediates these gradual changes. To determine how ventilation and oxygenation affect eNOS gene expression, 12 fetal lambs were ventilated for 8 h without changing fetal descending aortic blood gases or pH (rhythmic distension) or with 100% oxygen (O 2 ventilation). Vascular pressures and PBF were measured. Total RNA, protein, and tissue sections were prepared from lung tissue for RNase protection assays, Western blotting, and in situ hybridization. O 2 ventilation increased PBF and decreased PVR more than rhythmic distension ( P Ͻ 0.05). Rhythmic distension increased eNOS mRNA expression; O 2 ventilation increased eNOS mRNA expression more and increased eNOS protein expression ( P Ͻ 0.05). To define the mechanisms responsible for these changes, ovine fetal pulmonary arterial endothelial cells were exposed to 1, 21, or 95% O 2 or to shear stress. 95% O 2 increased eNOS mRNA and protein expression ( P Ͻ 0.05). Shear stress increased eNOS mRNA and protein expression ( P Ͻ 0.05). Increased oxygenation but more importantly increased PBF with increased shear stress induce eNOS gene expression and contribute to pulmonary vasodilation after birth. (

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“…Prostaglandins activate adenylate cyclase to increase cAMP concentrations in vascular smooth muscle cells (Figure 2). Cyclooxygenase-1 in particular is upregulated during late gestation, leading to an increase in prostacyclin production in the third trimester and early postnatal life [25,26]. Inhibition of prostacyclin production by non-steroidal anti-inflammatory drugs (NSAIDs) during late pregnancy has been associated with PPHN although this association has been recently called into question [27].…”

Section: Mediators Of Circulatory Transition At Birthmentioning

confidence: 99%

Persistent Pulmonary Hypertension of the Newborn

Nair

Bataclan²

1998

Key Topics in Neonatology

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Persistent pulmonary hypertension of the newborn (PPHN) is characterized by elevated pulmonary vascular resistance resulting in right-to-left shunting of blood and hypoxemia. PPHN is often secondary to parenchymal lung disease (such as meconium aspiration syndrome, pneumonia or respiratory distress syndrome) or lung hypoplasia (with congenital diaphragmatic hernia or oligohydramnios) but can also be idiopathic. The diagnosis of PPHN is based on clinical evidence of labile hypoxemia often associated with differential cyanosis. The diagnosis is confirmed by the echocardiographic demonstration of -(a) right-to-left or bidirectional shunt at the ductus or foramen ovale and/or, (b) flattening or leftward deviation of the interventricular septum and/or, (c) tricuspid regurgitation, and finally (d) absence of structural heart disease. Management strategies include optimal oxygenation, avoiding respiratory and metabolic acidosis, blood pressure stabilization, sedation and pulmonary vasodilator therapy. Failure of these measures would lead to consideration of extracorporeal membrane oxygenation (ECMO); however decreased need for this rescue therapy has been documented with advances in medical management. While trends also note improved survival, long-term neurodevelopmental disabilities such as deafness and learning disabilities remain a concern in many infants with severe PPHN. Funded by: 1R01HD072929-0 (SL)

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The Onset of Breathing at Birth Stimulates Pulmonary Vascular Prostacyclin Synthesis

Cited by 14 publications

References 14 publications

Physiologic characterization of endothelin A and B receptor activity in the ovine fetal pulmonary circulation.

Physiologic characterization of endothelin A and B receptor activity in the ovine fetal pulmonary circulation.

Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs.

Persistent Pulmonary Hypertension of the Newborn

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