Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and message

K. A. Hanson, F. Burns, S. D. Rybalkin, J. W. Miller, J. Beavo, W. R. Clarke

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

During transitional circulation, the pulmonary vascular bed undergoes a rapid and profound reduction in both tone and vascular smooth-muscle (VSM) content. 3',5'-Guanylate cyclic monophosphate (cGMP) is a crucial mediator in the regulation of pulmonary vascular resistance (PVR) and VSM proliferation. Hydrolysis of cGMP is achieved predominately by cGMP-specific phosphodiesterases (PDEs). Among the cGMP-specific PDEs, PDE5 is quantitatively prevalent in lung tissue. We have investigated the levels of pulmonary PDE5 enzymatic activity, protein, and messenger RNA (mRNA) in ovine and mouse lung during perinatal development. We report that within 1 h following birth, PDE5 activity, protein, and mRNA levels decrease in both species, in a manner that correlates with known decreases in PVR in early transition. However, from 4 to 7 d following birth, a secondary increase in PDE5 activity, protein, and mRNA occurs in both ovine and mouse lung, suggesting a complex regulation of PVR and VSM proliferation in late perinatal development. Our data imply that PDE5 may be an important mediator in the regulation of PVR in normal and possibly in pathologic states, and may ultimately provide a basis for PDE5 inhibitors as a treatment for pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)279-288
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume158
Issue number1
DOIs
StatePublished - Jan 1 1998

Fingerprint

Type 5 Cyclic Nucleotide Phosphodiesterases
Vascular Resistance
Lung
Vascular Smooth Muscle
Phosphoric Diester Hydrolases
Proteins
Messenger RNA
Sheep
Parturition
Phosphodiesterase 5 Inhibitors
Pulmonary Hypertension
Blood Vessels
Hydrolysis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and message. / Hanson, K. A.; Burns, F.; Rybalkin, S. D.; Miller, J. W.; Beavo, J.; Clarke, W. R.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 158, No. 1, 01.01.1998, p. 279-288.

Research output: Contribution to journalArticle

Hanson, K. A. ; Burns, F. ; Rybalkin, S. D. ; Miller, J. W. ; Beavo, J. ; Clarke, W. R. / Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and message. In: American Journal of Respiratory and Critical Care Medicine. 1998 ; Vol. 158, No. 1. pp. 279-288.
@article{4ffd949c6d5c439fa38150735f984721,
title = "Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and message",
abstract = "During transitional circulation, the pulmonary vascular bed undergoes a rapid and profound reduction in both tone and vascular smooth-muscle (VSM) content. 3',5'-Guanylate cyclic monophosphate (cGMP) is a crucial mediator in the regulation of pulmonary vascular resistance (PVR) and VSM proliferation. Hydrolysis of cGMP is achieved predominately by cGMP-specific phosphodiesterases (PDEs). Among the cGMP-specific PDEs, PDE5 is quantitatively prevalent in lung tissue. We have investigated the levels of pulmonary PDE5 enzymatic activity, protein, and messenger RNA (mRNA) in ovine and mouse lung during perinatal development. We report that within 1 h following birth, PDE5 activity, protein, and mRNA levels decrease in both species, in a manner that correlates with known decreases in PVR in early transition. However, from 4 to 7 d following birth, a secondary increase in PDE5 activity, protein, and mRNA occurs in both ovine and mouse lung, suggesting a complex regulation of PVR and VSM proliferation in late perinatal development. Our data imply that PDE5 may be an important mediator in the regulation of PVR in normal and possibly in pathologic states, and may ultimately provide a basis for PDE5 inhibitors as a treatment for pulmonary hypertension.",
author = "Hanson, {K. A.} and F. Burns and Rybalkin, {S. D.} and Miller, {J. W.} and J. Beavo and Clarke, {W. R.}",
year = "1998",
month = "1",
day = "1",
doi = "10.1164/ajrccm.158.1.9711042",
language = "English (US)",
volume = "158",
pages = "279--288",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "1",

}

TY - JOUR

T1 - Developmental changes in lung cGMP phosphodiesterase-5 activity, protein, and message

AU - Hanson, K. A.

AU - Burns, F.

AU - Rybalkin, S. D.

AU - Miller, J. W.

AU - Beavo, J.

AU - Clarke, W. R.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - During transitional circulation, the pulmonary vascular bed undergoes a rapid and profound reduction in both tone and vascular smooth-muscle (VSM) content. 3',5'-Guanylate cyclic monophosphate (cGMP) is a crucial mediator in the regulation of pulmonary vascular resistance (PVR) and VSM proliferation. Hydrolysis of cGMP is achieved predominately by cGMP-specific phosphodiesterases (PDEs). Among the cGMP-specific PDEs, PDE5 is quantitatively prevalent in lung tissue. We have investigated the levels of pulmonary PDE5 enzymatic activity, protein, and messenger RNA (mRNA) in ovine and mouse lung during perinatal development. We report that within 1 h following birth, PDE5 activity, protein, and mRNA levels decrease in both species, in a manner that correlates with known decreases in PVR in early transition. However, from 4 to 7 d following birth, a secondary increase in PDE5 activity, protein, and mRNA occurs in both ovine and mouse lung, suggesting a complex regulation of PVR and VSM proliferation in late perinatal development. Our data imply that PDE5 may be an important mediator in the regulation of PVR in normal and possibly in pathologic states, and may ultimately provide a basis for PDE5 inhibitors as a treatment for pulmonary hypertension.

AB - During transitional circulation, the pulmonary vascular bed undergoes a rapid and profound reduction in both tone and vascular smooth-muscle (VSM) content. 3',5'-Guanylate cyclic monophosphate (cGMP) is a crucial mediator in the regulation of pulmonary vascular resistance (PVR) and VSM proliferation. Hydrolysis of cGMP is achieved predominately by cGMP-specific phosphodiesterases (PDEs). Among the cGMP-specific PDEs, PDE5 is quantitatively prevalent in lung tissue. We have investigated the levels of pulmonary PDE5 enzymatic activity, protein, and messenger RNA (mRNA) in ovine and mouse lung during perinatal development. We report that within 1 h following birth, PDE5 activity, protein, and mRNA levels decrease in both species, in a manner that correlates with known decreases in PVR in early transition. However, from 4 to 7 d following birth, a secondary increase in PDE5 activity, protein, and mRNA occurs in both ovine and mouse lung, suggesting a complex regulation of PVR and VSM proliferation in late perinatal development. Our data imply that PDE5 may be an important mediator in the regulation of PVR in normal and possibly in pathologic states, and may ultimately provide a basis for PDE5 inhibitors as a treatment for pulmonary hypertension.

UR - http://www.scopus.com/inward/record.url?scp=0031846121&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031846121&partnerID=8YFLogxK

U2 - 10.1164/ajrccm.158.1.9711042

DO - 10.1164/ajrccm.158.1.9711042

M3 - Article

C2 - 9655741

AN - SCOPUS:0031846121

VL - 158

SP - 279

EP - 288

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 1

ER -