Regulation of ductus arteriosus patency by nitric oxide in fetal lambs

The role of gestation, oxygen tension, and vasa vasorum

Ronald I. Clyman, Nahid Waleh, Stephen Matthew Black, R. Kirk Rlemer, Françoise Mauray, Yao Qi Chen

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

We hypothesized that nitric oxide (NO) production by the fetal ductus arteriosus is limited because of low fetal Po2, but that at neonatal Po2, NO might be an important regulator of ductus arteriosus tone. We exposed isolated rings of fetal lamb ductus arteriosus to elevated Po2. t.-N-nitro- L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and methylene blue and 6-anilino-5,8-quinolinedione (LY83583), inhibitors of guanylate cyclase, produced constriction of the ductus arteriosus. When ductus arteriosus rings were exposed to low Po2, L-NAME had no effect, and methylene blue and LY83583 had only a small effect on ductus arteriosus tone. Sodium nitroprusside and calcium ionophore A23187 relaxed ductus arteriosus rings more than aortic rings, and relaxed ductus arteriosus rings from immature fetuses more than those from late gestation fetuses. In contrast, ductus arteriosus rings from both early and late gestation were equally sensitive to 8-bromo-cGMP. By both reverse transcriptase-polymerase chain reaction and immunohistochemistry, endothelial cell NOS and inducible calcium-independent NOS, but not nerve cell NOS, were detected in the ductus arteriosus. Inducible NOS was expressed only by endothelial cells lining the ductus arteriosus lumen; in contrast, endothelial cell NOS was expressed by both luminal and vasa vasorum endothelial cells. The role of inducible NOS in the ductus arteriosus is uncertain because the potency of a specific inducible NOS inhibitor in constricting the ductus arteriosus was negligible compared with that of an endothelial cell NOS inhibitor. We speculate that NO may be an important regulator of ductus arteriosus tone at high but not low Po2. The endothelial cell NOS isoform found in vasa vasorum may be an important source of NO because removal of ductus arteriosus luminal endothelium only partially blocks the effects of L-NAME, methylene blue, and LY83583.

Original languageEnglish (US)
Pages (from-to)633-644
Number of pages12
JournalPediatric Research
Volume43
Issue number5
DOIs
StatePublished - Jan 1 1998

Fingerprint

Vasa Vasorum
Ductus Arteriosus
Patent Ductus Arteriosus
Nitric Oxide
Oxygen
Pregnancy
6-anilino-5,8-quinolinedione
Endothelial Cells
Nitric Oxide Synthase Type III
Methylene Blue
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase Type II
Nitric Oxide Synthase
Sodium Ionophores
Fetus
Calcium Ionophores
Guanylate Cyclase

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Regulation of ductus arteriosus patency by nitric oxide in fetal lambs : The role of gestation, oxygen tension, and vasa vasorum. / Clyman, Ronald I.; Waleh, Nahid; Black, Stephen Matthew; Kirk Rlemer, R.; Mauray, Françoise; Chen, Yao Qi.

In: Pediatric Research, Vol. 43, No. 5, 01.01.1998, p. 633-644.

Research output: Contribution to journalArticle

Clyman, Ronald I. ; Waleh, Nahid ; Black, Stephen Matthew ; Kirk Rlemer, R. ; Mauray, Françoise ; Chen, Yao Qi. / Regulation of ductus arteriosus patency by nitric oxide in fetal lambs : The role of gestation, oxygen tension, and vasa vasorum. In: Pediatric Research. 1998 ; Vol. 43, No. 5. pp. 633-644.
@article{1f7ea15a398c42d1aea2cc2cf7d2db48,
title = "Regulation of ductus arteriosus patency by nitric oxide in fetal lambs: The role of gestation, oxygen tension, and vasa vasorum",
abstract = "We hypothesized that nitric oxide (NO) production by the fetal ductus arteriosus is limited because of low fetal Po2, but that at neonatal Po2, NO might be an important regulator of ductus arteriosus tone. We exposed isolated rings of fetal lamb ductus arteriosus to elevated Po2. t.-N-nitro- L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and methylene blue and 6-anilino-5,8-quinolinedione (LY83583), inhibitors of guanylate cyclase, produced constriction of the ductus arteriosus. When ductus arteriosus rings were exposed to low Po2, L-NAME had no effect, and methylene blue and LY83583 had only a small effect on ductus arteriosus tone. Sodium nitroprusside and calcium ionophore A23187 relaxed ductus arteriosus rings more than aortic rings, and relaxed ductus arteriosus rings from immature fetuses more than those from late gestation fetuses. In contrast, ductus arteriosus rings from both early and late gestation were equally sensitive to 8-bromo-cGMP. By both reverse transcriptase-polymerase chain reaction and immunohistochemistry, endothelial cell NOS and inducible calcium-independent NOS, but not nerve cell NOS, were detected in the ductus arteriosus. Inducible NOS was expressed only by endothelial cells lining the ductus arteriosus lumen; in contrast, endothelial cell NOS was expressed by both luminal and vasa vasorum endothelial cells. The role of inducible NOS in the ductus arteriosus is uncertain because the potency of a specific inducible NOS inhibitor in constricting the ductus arteriosus was negligible compared with that of an endothelial cell NOS inhibitor. We speculate that NO may be an important regulator of ductus arteriosus tone at high but not low Po2. The endothelial cell NOS isoform found in vasa vasorum may be an important source of NO because removal of ductus arteriosus luminal endothelium only partially blocks the effects of L-NAME, methylene blue, and LY83583.",
author = "Clyman, {Ronald I.} and Nahid Waleh and Black, {Stephen Matthew} and {Kirk Rlemer}, R. and Fran{\cc}oise Mauray and Chen, {Yao Qi}",
year = "1998",
month = "1",
day = "1",
doi = "10.1203/00006450-199805000-00012",
language = "English (US)",
volume = "43",
pages = "633--644",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Regulation of ductus arteriosus patency by nitric oxide in fetal lambs

T2 - The role of gestation, oxygen tension, and vasa vasorum

AU - Clyman, Ronald I.

AU - Waleh, Nahid

AU - Black, Stephen Matthew

AU - Kirk Rlemer, R.

AU - Mauray, Françoise

AU - Chen, Yao Qi

PY - 1998/1/1

Y1 - 1998/1/1

N2 - We hypothesized that nitric oxide (NO) production by the fetal ductus arteriosus is limited because of low fetal Po2, but that at neonatal Po2, NO might be an important regulator of ductus arteriosus tone. We exposed isolated rings of fetal lamb ductus arteriosus to elevated Po2. t.-N-nitro- L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and methylene blue and 6-anilino-5,8-quinolinedione (LY83583), inhibitors of guanylate cyclase, produced constriction of the ductus arteriosus. When ductus arteriosus rings were exposed to low Po2, L-NAME had no effect, and methylene blue and LY83583 had only a small effect on ductus arteriosus tone. Sodium nitroprusside and calcium ionophore A23187 relaxed ductus arteriosus rings more than aortic rings, and relaxed ductus arteriosus rings from immature fetuses more than those from late gestation fetuses. In contrast, ductus arteriosus rings from both early and late gestation were equally sensitive to 8-bromo-cGMP. By both reverse transcriptase-polymerase chain reaction and immunohistochemistry, endothelial cell NOS and inducible calcium-independent NOS, but not nerve cell NOS, were detected in the ductus arteriosus. Inducible NOS was expressed only by endothelial cells lining the ductus arteriosus lumen; in contrast, endothelial cell NOS was expressed by both luminal and vasa vasorum endothelial cells. The role of inducible NOS in the ductus arteriosus is uncertain because the potency of a specific inducible NOS inhibitor in constricting the ductus arteriosus was negligible compared with that of an endothelial cell NOS inhibitor. We speculate that NO may be an important regulator of ductus arteriosus tone at high but not low Po2. The endothelial cell NOS isoform found in vasa vasorum may be an important source of NO because removal of ductus arteriosus luminal endothelium only partially blocks the effects of L-NAME, methylene blue, and LY83583.

AB - We hypothesized that nitric oxide (NO) production by the fetal ductus arteriosus is limited because of low fetal Po2, but that at neonatal Po2, NO might be an important regulator of ductus arteriosus tone. We exposed isolated rings of fetal lamb ductus arteriosus to elevated Po2. t.-N-nitro- L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and methylene blue and 6-anilino-5,8-quinolinedione (LY83583), inhibitors of guanylate cyclase, produced constriction of the ductus arteriosus. When ductus arteriosus rings were exposed to low Po2, L-NAME had no effect, and methylene blue and LY83583 had only a small effect on ductus arteriosus tone. Sodium nitroprusside and calcium ionophore A23187 relaxed ductus arteriosus rings more than aortic rings, and relaxed ductus arteriosus rings from immature fetuses more than those from late gestation fetuses. In contrast, ductus arteriosus rings from both early and late gestation were equally sensitive to 8-bromo-cGMP. By both reverse transcriptase-polymerase chain reaction and immunohistochemistry, endothelial cell NOS and inducible calcium-independent NOS, but not nerve cell NOS, were detected in the ductus arteriosus. Inducible NOS was expressed only by endothelial cells lining the ductus arteriosus lumen; in contrast, endothelial cell NOS was expressed by both luminal and vasa vasorum endothelial cells. The role of inducible NOS in the ductus arteriosus is uncertain because the potency of a specific inducible NOS inhibitor in constricting the ductus arteriosus was negligible compared with that of an endothelial cell NOS inhibitor. We speculate that NO may be an important regulator of ductus arteriosus tone at high but not low Po2. The endothelial cell NOS isoform found in vasa vasorum may be an important source of NO because removal of ductus arteriosus luminal endothelium only partially blocks the effects of L-NAME, methylene blue, and LY83583.

UR - http://www.scopus.com/inward/record.url?scp=0031980250&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031980250&partnerID=8YFLogxK

U2 - 10.1203/00006450-199805000-00012

DO - 10.1203/00006450-199805000-00012

M3 - Article

VL - 43

SP - 633

EP - 644

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 5

ER -