Regulation of phosphodiesterase 3 in the pulmonary arteries during the perinatal period in sheep

Bernadette Chen, Satyanarayana Lakshminrusimha, Lyubov Czech, Beezly S. Groh, Sylvia F. Gugino, James A. Russell, Kathryn N. Farrow, Robin H Steinhorn

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The role of cAMP in the pulmonary vasculature during the transition from intrauterine to extrauterine life is poorly understood. We hypothesized that cAMP levels are regulated by alterations in phosphodiesterase 3 (PDE3), which hydrolyzes cAMP. PDE3 protein expression and hydrolytic activity were increased in the resistance pulmonary arteries (PA) from spontaneously breathing 1-d-old (1dSB) lambs relative to equivalent-gestation fetuses. This was accompanied by a decrease in steady-state cAMP. Ventilation with 21% O2 and 100% O2 for 24 h disrupted the normal transition, whereas ventilation with 100% O2 + inhaled NO (iNO) for 24 h restored both PDE3 activity and cAMP to 1dSB levels. Consistent with these findings, relaxation to milrinone, a PDE3 inhibitor, was greater in the PA isolated from 1dSB and 100% O2 + iNO lambs, relative to fetal, 21% O2, and 100% O2 lambs. In conclusion, PDE3 expression and activity in the PA dramatically increase after birth, with a concomitant decrease in steady-state cAMP. Ventilation with either 21% O2 or 100% O2 blunts this PDE3 increase, whereas iNO restores PDE3 activity to levels equivalent to 1dSB lambs. The vasodilatory effects of milrinone were most pronounced in vessels from lambs with the highest PDE3 activity, i.e., 1dSB and 100% O2 + iNO lambs. Thus, milrinone may be most beneficial when used in conjunction with iNO.

Original languageEnglish (US)
Pages (from-to)682-687
Number of pages6
JournalPediatric Research
Volume66
Issue number6
DOIs
StatePublished - Dec 2009
Externally publishedYes

Fingerprint

Phosphoric Diester Hydrolases
Pulmonary Artery
Sheep
Milrinone
Ventilation
Phosphodiesterase 3 Inhibitors
Respiration
Fetus
Parturition
Pregnancy
Lung
Proteins

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Regulation of phosphodiesterase 3 in the pulmonary arteries during the perinatal period in sheep. / Chen, Bernadette; Lakshminrusimha, Satyanarayana; Czech, Lyubov; Groh, Beezly S.; Gugino, Sylvia F.; Russell, James A.; Farrow, Kathryn N.; Steinhorn, Robin H.

In: Pediatric Research, Vol. 66, No. 6, 12.2009, p. 682-687.

Research output: Contribution to journalArticle

Chen, B, Lakshminrusimha, S, Czech, L, Groh, BS, Gugino, SF, Russell, JA, Farrow, KN & Steinhorn, RH 2009, 'Regulation of phosphodiesterase 3 in the pulmonary arteries during the perinatal period in sheep', Pediatric Research, vol. 66, no. 6, pp. 682-687. https://doi.org/10.1203/PDR.0b013e3181bce574
Chen, Bernadette ; Lakshminrusimha, Satyanarayana ; Czech, Lyubov ; Groh, Beezly S. ; Gugino, Sylvia F. ; Russell, James A. ; Farrow, Kathryn N. ; Steinhorn, Robin H. / Regulation of phosphodiesterase 3 in the pulmonary arteries during the perinatal period in sheep. In: Pediatric Research. 2009 ; Vol. 66, No. 6. pp. 682-687.
@article{01b103f176f14c0c855554617f130c6a,
title = "Regulation of phosphodiesterase 3 in the pulmonary arteries during the perinatal period in sheep",
abstract = "The role of cAMP in the pulmonary vasculature during the transition from intrauterine to extrauterine life is poorly understood. We hypothesized that cAMP levels are regulated by alterations in phosphodiesterase 3 (PDE3), which hydrolyzes cAMP. PDE3 protein expression and hydrolytic activity were increased in the resistance pulmonary arteries (PA) from spontaneously breathing 1-d-old (1dSB) lambs relative to equivalent-gestation fetuses. This was accompanied by a decrease in steady-state cAMP. Ventilation with 21{\%} O2 and 100{\%} O2 for 24 h disrupted the normal transition, whereas ventilation with 100{\%} O2 + inhaled NO (iNO) for 24 h restored both PDE3 activity and cAMP to 1dSB levels. Consistent with these findings, relaxation to milrinone, a PDE3 inhibitor, was greater in the PA isolated from 1dSB and 100{\%} O2 + iNO lambs, relative to fetal, 21{\%} O2, and 100{\%} O2 lambs. In conclusion, PDE3 expression and activity in the PA dramatically increase after birth, with a concomitant decrease in steady-state cAMP. Ventilation with either 21{\%} O2 or 100{\%} O2 blunts this PDE3 increase, whereas iNO restores PDE3 activity to levels equivalent to 1dSB lambs. The vasodilatory effects of milrinone were most pronounced in vessels from lambs with the highest PDE3 activity, i.e., 1dSB and 100{\%} O2 + iNO lambs. Thus, milrinone may be most beneficial when used in conjunction with iNO.",
author = "Bernadette Chen and Satyanarayana Lakshminrusimha and Lyubov Czech and Groh, {Beezly S.} and Gugino, {Sylvia F.} and Russell, {James A.} and Farrow, {Kathryn N.} and Steinhorn, {Robin H}",
year = "2009",
month = "12",
doi = "10.1203/PDR.0b013e3181bce574",
language = "English (US)",
volume = "66",
pages = "682--687",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Regulation of phosphodiesterase 3 in the pulmonary arteries during the perinatal period in sheep

AU - Chen, Bernadette

AU - Lakshminrusimha, Satyanarayana

AU - Czech, Lyubov

AU - Groh, Beezly S.

AU - Gugino, Sylvia F.

AU - Russell, James A.

AU - Farrow, Kathryn N.

AU - Steinhorn, Robin H

PY - 2009/12

Y1 - 2009/12

N2 - The role of cAMP in the pulmonary vasculature during the transition from intrauterine to extrauterine life is poorly understood. We hypothesized that cAMP levels are regulated by alterations in phosphodiesterase 3 (PDE3), which hydrolyzes cAMP. PDE3 protein expression and hydrolytic activity were increased in the resistance pulmonary arteries (PA) from spontaneously breathing 1-d-old (1dSB) lambs relative to equivalent-gestation fetuses. This was accompanied by a decrease in steady-state cAMP. Ventilation with 21% O2 and 100% O2 for 24 h disrupted the normal transition, whereas ventilation with 100% O2 + inhaled NO (iNO) for 24 h restored both PDE3 activity and cAMP to 1dSB levels. Consistent with these findings, relaxation to milrinone, a PDE3 inhibitor, was greater in the PA isolated from 1dSB and 100% O2 + iNO lambs, relative to fetal, 21% O2, and 100% O2 lambs. In conclusion, PDE3 expression and activity in the PA dramatically increase after birth, with a concomitant decrease in steady-state cAMP. Ventilation with either 21% O2 or 100% O2 blunts this PDE3 increase, whereas iNO restores PDE3 activity to levels equivalent to 1dSB lambs. The vasodilatory effects of milrinone were most pronounced in vessels from lambs with the highest PDE3 activity, i.e., 1dSB and 100% O2 + iNO lambs. Thus, milrinone may be most beneficial when used in conjunction with iNO.

AB - The role of cAMP in the pulmonary vasculature during the transition from intrauterine to extrauterine life is poorly understood. We hypothesized that cAMP levels are regulated by alterations in phosphodiesterase 3 (PDE3), which hydrolyzes cAMP. PDE3 protein expression and hydrolytic activity were increased in the resistance pulmonary arteries (PA) from spontaneously breathing 1-d-old (1dSB) lambs relative to equivalent-gestation fetuses. This was accompanied by a decrease in steady-state cAMP. Ventilation with 21% O2 and 100% O2 for 24 h disrupted the normal transition, whereas ventilation with 100% O2 + inhaled NO (iNO) for 24 h restored both PDE3 activity and cAMP to 1dSB levels. Consistent with these findings, relaxation to milrinone, a PDE3 inhibitor, was greater in the PA isolated from 1dSB and 100% O2 + iNO lambs, relative to fetal, 21% O2, and 100% O2 lambs. In conclusion, PDE3 expression and activity in the PA dramatically increase after birth, with a concomitant decrease in steady-state cAMP. Ventilation with either 21% O2 or 100% O2 blunts this PDE3 increase, whereas iNO restores PDE3 activity to levels equivalent to 1dSB lambs. The vasodilatory effects of milrinone were most pronounced in vessels from lambs with the highest PDE3 activity, i.e., 1dSB and 100% O2 + iNO lambs. Thus, milrinone may be most beneficial when used in conjunction with iNO.

UR - http://www.scopus.com/inward/record.url?scp=73449095428&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73449095428&partnerID=8YFLogxK

U2 - 10.1203/PDR.0b013e3181bce574

DO - 10.1203/PDR.0b013e3181bce574

M3 - Article

C2 - 19707176

AN - SCOPUS:73449095428

VL - 66

SP - 682

EP - 687

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 6

ER -