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cGMP-Dependent Protein Kinase in Regulation of the Perinatal Pulmonary Circulation

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Cell Signaling in Vascular Inflammation

Abstract

At birth, the increase in oxygen tension results in upregulation of the nitric oxide-cGMP pathway in the pulmonary vasculature and facilitates vasodilation and a fall in pulmonary vascular resistance. In the perinatal period, both cAMP and cyclic guanosine monophosphate (cGMP) act via cGMP-dependent protein kinase (PKG) in mediating relaxation of the pulmonary circulation, with cGMP working predominantly via PKG. Oxygen exposure results in an increase in PKG activity, PKG protein content, and mRNA expression in fetal pulmonary vascular smooth muscle. The increased production of reactive oxygen species in pulmonary vascular smooth muscle that occurs during hypoxia in the fetus is responsible for downregulation of PKG activity and the PKG protein levels in pulmonary vascular smooth muscle in the fetus, which is reversed on exposure to increased oxygen tension at birth. PKG mRNA expression also appears to be regulated by nitric oxide and cGMP, such that chronic exposure of pulmonary vascular smooth muscle to nitric oxide and cGMP results in downregulation of PKG mRNA levels. This might be one mechanism by which chronic inhalation therapy with nitric oxide in neonates with persistent pulmonary hypertension of the newborn results in development of resistance to nitric oxide-mediated vasodilation in the pulmonary circulation.

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Authors and Affiliations

  1. Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, USA

    Usha Raj MD, Yuansheng Gao MD, Srinivas Dhanakoti Phd & Fred Sander BS

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  1. Usha Raj MD
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  2. Yuansheng Gao MD
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  3. Srinivas Dhanakoti Phd
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  1. Clinical Physiological Medicine, and Medicine, Columbia University, New York, NY, USA

    Jahar Bhattacharya MBBS, DPhil (Professor of Physiology and Cellular Biophysics) (Professor of Physiology and Cellular Biophysics)

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Raj, U., Gao, Y., Dhanakoti, S., Sander, F. (2005). cGMP-Dependent Protein Kinase in Regulation of the Perinatal Pulmonary Circulation. In: Bhattacharya, J. (eds) Cell Signaling in Vascular Inflammation. Humana Press. https://doi.org/10.1007/978-1-59259-909-7_5

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