Contractile properties of intralobar pulmonary arteries and veins in the fetal lamb model of congenital diaphragmatic hernia

Michael S. Irish, Philip L. Glick, James Russell, Pierina Kapur, Daniel A. Bambini, Bruce A. Holm, Robin H Steinhorn

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background/Purpose: Pulmonary hypertension plays a significant role in the pathophysiology of congenital diaphragmatic hernia (CDH). Although there has been an intensive research effort directed at mediators that may cause pulmonary vasoconstriction, no single agent has been identified. The authors hypothesize that there may be an alteration in the cGMP-nitric oxide (NO) pathway of vasodilatation contributing to the pulmonary hypertension observed in CDH. The purpose of these studies is to begin to elucidate vasoactive properties of pulmonary vessels with particular attention to the cGMP-NO pathway of vasodilatation in fetal lambs with CDH. Methods: Fourth-generation pulmonary arteries and pulmonary veins were dissected from both right and left lungs of eight, 139-day gestational fetuses with surgically created CDH. Vessels were studied with standard isolated tissue bath techniques. Experiments examined basal release of NO in endothelium-intact PVs and PAs of both right and left lungs by measuring the contractile force of vessels constricted with norepinephrine (NE) in the presence and absence of the nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine (L-NA). Concentration-response curves to the vasodilating agents zaprinast and A23187 were also obtained in vessels contracted by NE. Results: Left and right pulmonary artery responses to NE are enhanced over those of historic controls. Pretreatment of left pulmonary arteries with L-NA enhances the vasoconstrictor response to NE, whereas right PAs show no increased response. Relaxation responses to A23187 and zaprinast, in both left and right pulmonary arteries were not different from control lambs. Relaxation responses of both left and right pulmonary veins to A23187 and zaprinast are blunted compared with controls. This blunting is significantly more in left pulmonary veins than right. Further, right but not left pulmonary veins display enhanced vasoconstrictive response to NE after L-NA pretreatment. Conclusions: The NO-cGMP pathway of vasodilatation is abnormal in the near term, fetal lamb with CDH. These abnormalities were most apparent in pulmonary veins and may reflect abnormal NOS activity or content between left and right lungs of the fetal lamb with CDH. Pulmonary arteries from CDH lambs have basal and stimulated NO release equal to that of historic controls but appear to be hypersensitive to exogenous vasoconstrictors.

Original languageEnglish (US)
Pages (from-to)921-928
Number of pages8
JournalJournal of Pediatric Surgery
Volume33
Issue number6
DOIs
StatePublished - Jun 1998
Externally publishedYes

Fingerprint

Pulmonary Veins
Pulmonary Artery
Norepinephrine
Nitric Oxide
Calcimycin
Lung
Vasodilation
Vasoconstrictor Agents
Pulmonary Hypertension
Nitric Oxide Synthase
Congenital Diaphragmatic Hernias
Vasoconstriction
Baths
Endothelium
Arginine
Fetus
Research
zaprinast

Keywords

  • A23187
  • Congenital diaphragmatic hernia
  • Guanylate cyclase
  • Nω-nitro-L-arginine
  • Nitric oxide
  • Persistent pulmonary hypertension
  • Phosphodiesterase inhibitor
  • Transitional circulation
  • Vascular smooth muscle
  • Zaprinast

ASJC Scopus subject areas

  • Surgery

Cite this

Contractile properties of intralobar pulmonary arteries and veins in the fetal lamb model of congenital diaphragmatic hernia. / Irish, Michael S.; Glick, Philip L.; Russell, James; Kapur, Pierina; Bambini, Daniel A.; Holm, Bruce A.; Steinhorn, Robin H.

In: Journal of Pediatric Surgery, Vol. 33, No. 6, 06.1998, p. 921-928.

Research output: Contribution to journalArticle

Irish, Michael S. ; Glick, Philip L. ; Russell, James ; Kapur, Pierina ; Bambini, Daniel A. ; Holm, Bruce A. ; Steinhorn, Robin H. / Contractile properties of intralobar pulmonary arteries and veins in the fetal lamb model of congenital diaphragmatic hernia. In: Journal of Pediatric Surgery. 1998 ; Vol. 33, No. 6. pp. 921-928.
@article{28ef309d7c6f4e0c8c5d19c3fb629f61,
title = "Contractile properties of intralobar pulmonary arteries and veins in the fetal lamb model of congenital diaphragmatic hernia",
abstract = "Background/Purpose: Pulmonary hypertension plays a significant role in the pathophysiology of congenital diaphragmatic hernia (CDH). Although there has been an intensive research effort directed at mediators that may cause pulmonary vasoconstriction, no single agent has been identified. The authors hypothesize that there may be an alteration in the cGMP-nitric oxide (NO) pathway of vasodilatation contributing to the pulmonary hypertension observed in CDH. The purpose of these studies is to begin to elucidate vasoactive properties of pulmonary vessels with particular attention to the cGMP-NO pathway of vasodilatation in fetal lambs with CDH. Methods: Fourth-generation pulmonary arteries and pulmonary veins were dissected from both right and left lungs of eight, 139-day gestational fetuses with surgically created CDH. Vessels were studied with standard isolated tissue bath techniques. Experiments examined basal release of NO in endothelium-intact PVs and PAs of both right and left lungs by measuring the contractile force of vessels constricted with norepinephrine (NE) in the presence and absence of the nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine (L-NA). Concentration-response curves to the vasodilating agents zaprinast and A23187 were also obtained in vessels contracted by NE. Results: Left and right pulmonary artery responses to NE are enhanced over those of historic controls. Pretreatment of left pulmonary arteries with L-NA enhances the vasoconstrictor response to NE, whereas right PAs show no increased response. Relaxation responses to A23187 and zaprinast, in both left and right pulmonary arteries were not different from control lambs. Relaxation responses of both left and right pulmonary veins to A23187 and zaprinast are blunted compared with controls. This blunting is significantly more in left pulmonary veins than right. Further, right but not left pulmonary veins display enhanced vasoconstrictive response to NE after L-NA pretreatment. Conclusions: The NO-cGMP pathway of vasodilatation is abnormal in the near term, fetal lamb with CDH. These abnormalities were most apparent in pulmonary veins and may reflect abnormal NOS activity or content between left and right lungs of the fetal lamb with CDH. Pulmonary arteries from CDH lambs have basal and stimulated NO release equal to that of historic controls but appear to be hypersensitive to exogenous vasoconstrictors.",
keywords = "A23187, Congenital diaphragmatic hernia, Guanylate cyclase, Nω-nitro-L-arginine, Nitric oxide, Persistent pulmonary hypertension, Phosphodiesterase inhibitor, Transitional circulation, Vascular smooth muscle, Zaprinast",
author = "Irish, {Michael S.} and Glick, {Philip L.} and James Russell and Pierina Kapur and Bambini, {Daniel A.} and Holm, {Bruce A.} and Steinhorn, {Robin H}",
year = "1998",
month = "6",
doi = "10.1016/S0022-3468(98)90675-3",
language = "English (US)",
volume = "33",
pages = "921--928",
journal = "Journal of Pediatric Surgery",
issn = "0022-3468",
publisher = "W.B. Saunders Ltd",
number = "6",

}

TY - JOUR

T1 - Contractile properties of intralobar pulmonary arteries and veins in the fetal lamb model of congenital diaphragmatic hernia

AU - Irish, Michael S.

AU - Glick, Philip L.

AU - Russell, James

AU - Kapur, Pierina

AU - Bambini, Daniel A.

AU - Holm, Bruce A.

AU - Steinhorn, Robin H

PY - 1998/6

Y1 - 1998/6

N2 - Background/Purpose: Pulmonary hypertension plays a significant role in the pathophysiology of congenital diaphragmatic hernia (CDH). Although there has been an intensive research effort directed at mediators that may cause pulmonary vasoconstriction, no single agent has been identified. The authors hypothesize that there may be an alteration in the cGMP-nitric oxide (NO) pathway of vasodilatation contributing to the pulmonary hypertension observed in CDH. The purpose of these studies is to begin to elucidate vasoactive properties of pulmonary vessels with particular attention to the cGMP-NO pathway of vasodilatation in fetal lambs with CDH. Methods: Fourth-generation pulmonary arteries and pulmonary veins were dissected from both right and left lungs of eight, 139-day gestational fetuses with surgically created CDH. Vessels were studied with standard isolated tissue bath techniques. Experiments examined basal release of NO in endothelium-intact PVs and PAs of both right and left lungs by measuring the contractile force of vessels constricted with norepinephrine (NE) in the presence and absence of the nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine (L-NA). Concentration-response curves to the vasodilating agents zaprinast and A23187 were also obtained in vessels contracted by NE. Results: Left and right pulmonary artery responses to NE are enhanced over those of historic controls. Pretreatment of left pulmonary arteries with L-NA enhances the vasoconstrictor response to NE, whereas right PAs show no increased response. Relaxation responses to A23187 and zaprinast, in both left and right pulmonary arteries were not different from control lambs. Relaxation responses of both left and right pulmonary veins to A23187 and zaprinast are blunted compared with controls. This blunting is significantly more in left pulmonary veins than right. Further, right but not left pulmonary veins display enhanced vasoconstrictive response to NE after L-NA pretreatment. Conclusions: The NO-cGMP pathway of vasodilatation is abnormal in the near term, fetal lamb with CDH. These abnormalities were most apparent in pulmonary veins and may reflect abnormal NOS activity or content between left and right lungs of the fetal lamb with CDH. Pulmonary arteries from CDH lambs have basal and stimulated NO release equal to that of historic controls but appear to be hypersensitive to exogenous vasoconstrictors.

AB - Background/Purpose: Pulmonary hypertension plays a significant role in the pathophysiology of congenital diaphragmatic hernia (CDH). Although there has been an intensive research effort directed at mediators that may cause pulmonary vasoconstriction, no single agent has been identified. The authors hypothesize that there may be an alteration in the cGMP-nitric oxide (NO) pathway of vasodilatation contributing to the pulmonary hypertension observed in CDH. The purpose of these studies is to begin to elucidate vasoactive properties of pulmonary vessels with particular attention to the cGMP-NO pathway of vasodilatation in fetal lambs with CDH. Methods: Fourth-generation pulmonary arteries and pulmonary veins were dissected from both right and left lungs of eight, 139-day gestational fetuses with surgically created CDH. Vessels were studied with standard isolated tissue bath techniques. Experiments examined basal release of NO in endothelium-intact PVs and PAs of both right and left lungs by measuring the contractile force of vessels constricted with norepinephrine (NE) in the presence and absence of the nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine (L-NA). Concentration-response curves to the vasodilating agents zaprinast and A23187 were also obtained in vessels contracted by NE. Results: Left and right pulmonary artery responses to NE are enhanced over those of historic controls. Pretreatment of left pulmonary arteries with L-NA enhances the vasoconstrictor response to NE, whereas right PAs show no increased response. Relaxation responses to A23187 and zaprinast, in both left and right pulmonary arteries were not different from control lambs. Relaxation responses of both left and right pulmonary veins to A23187 and zaprinast are blunted compared with controls. This blunting is significantly more in left pulmonary veins than right. Further, right but not left pulmonary veins display enhanced vasoconstrictive response to NE after L-NA pretreatment. Conclusions: The NO-cGMP pathway of vasodilatation is abnormal in the near term, fetal lamb with CDH. These abnormalities were most apparent in pulmonary veins and may reflect abnormal NOS activity or content between left and right lungs of the fetal lamb with CDH. Pulmonary arteries from CDH lambs have basal and stimulated NO release equal to that of historic controls but appear to be hypersensitive to exogenous vasoconstrictors.

KW - A23187

KW - Congenital diaphragmatic hernia

KW - Guanylate cyclase

KW - Nω-nitro-L-arginine

KW - Nitric oxide

KW - Persistent pulmonary hypertension

KW - Phosphodiesterase inhibitor

KW - Transitional circulation

KW - Vascular smooth muscle

KW - Zaprinast

UR - http://www.scopus.com/inward/record.url?scp=0031867033&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031867033&partnerID=8YFLogxK

U2 - 10.1016/S0022-3468(98)90675-3

DO - 10.1016/S0022-3468(98)90675-3

M3 - Article

C2 - 9660230

AN - SCOPUS:0031867033

VL - 33

SP - 921

EP - 928

JO - Journal of Pediatric Surgery

JF - Journal of Pediatric Surgery

SN - 0022-3468

IS - 6

ER -