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Phosphodiesterases as Drug Targets pp 251–277Cite as

Phosphodiesterases: Emerging Therapeutic Targets for Neonatal Pulmonary Hypertension

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 204))

Abstract

Pulmonary hypertension in the neonate is associated with multiple underlying problems such as respiratory distress syndrome, meconium aspiration syndrome, congenital diaphragmatic hernia, bronchopulmonary dysplasia, sepsis, or congenital heart disease. Because of the heterogeneous group of disorders, the therapeutic approach and response often depends on the underlying disease. In many of these conditions, there is evidence that cyclic nucleotide signaling and specifically phosphodiesterases (PDEs) are disrupted. PDE inhibitors represent an emerging class of pulmonary vasodilators in adults. Studies are now under way to evaluate the utility, efficacy, and safety of such therapies in infants with pulmonary hypertension.

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Abbreviations

BPD:

Bronchopulmonary dysplasia

CDH:

Congenital diaphragmatic hernia

COX:

Cyclooxygenase

eNOS:

Endothelial nitric oxide synthase

ET-1:

Endothelin-1

FPASMC:

Fetal pulmonary artery smooth muscle cells

H2O2 :

Hydrogen peroxide

iNOS:

Inducible nitric oxide synthase

iNO:

Inhaled nitric oxide

MAS:

Meconium aspiration syndrome

NAC:

N-acetyl-cysteine

NSAIDs:

Nonsteroidal anti-inflammatory drugs

PPHN:

Persistent pulmonary hypertension of the newborn

PDE:

Phosphodiesterase

PGIS:

Prostacyclin synthase

ROS:

Reactive oxygen species

RVH:

Right ventricular hypertrophy

sGC:

Soluble guanylate cyclase

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Acknowledgments

The authors are supported by NIH grants HL086715 (KNF) and HL54705 (RHS).

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Authors and Affiliations

  1. Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine, 310 E. Superior St., Morton 4-685D, Chicago, IL, 60611, USA

    Kathryn N. Farrow

  2. Division of Neonatology, Children’s Memorial Hospital and Northwestern University, 2300 Children’s Plaza #45, Chicago, IL, 60611, USA

    Robin H. Steinhorn

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  1. Kathryn N. Farrow
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  2. Robin H. Steinhorn
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Correspondence to Kathryn N. Farrow .

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Editors and Affiliations

  1. School of Medicine, Dept. Molecular Physiology & Biophysics, Vanderbilt University, Light Hall 702, Nashville, 37232-0615, Tennessee, USA

    Sharron H. Francis

  2. HSW 1656, Center for Reproductive Sciences, Parnassus Avenue 513, San Francisco, 94143-0556, California, USA

    Marco Conti

  3. Wolfson Building, University of Glasgow, Glasgow, G12 8QQ, United Kingdom

    Miles D. Houslay

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Farrow, K.N., Steinhorn, R.H. (2011). Phosphodiesterases: Emerging Therapeutic Targets for Neonatal Pulmonary Hypertension. In: Francis, S., Conti, M., Houslay, M. (eds) Phosphodiesterases as Drug Targets. Handbook of Experimental Pharmacology, vol 204. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-17969-3_11

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