Endothelial monocyte-activating polypeptide II causes NOS-dependent pulmonary artery vasodilation: A novel effect for a proinflammatory cytokine

Ben M. Tsai, Meijing Wang, Matthias Clauss, Peichuan Sun, Daniel R. Meldrum

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19 Citations (Scopus)

Abstract

Endothelial monocyte-activating polypeptide (EMAP) II is a novel proinflammatory cytokine that is released from apoptotic and hypoxic cells. The purpose of this study was to determine the effect of EMAP II on the pulmonary artery (PA) and to characterize its mechanism of action. To study this, isolated PA rings from adult male Sprague-Dawley rats were suspended on steel hooks connected to force transducers and immersed in 37°C organ baths containing modified Krebs-Henseleit solution. After equilibration, force displacement of phenylephrine-preconstricted PA was measured in response to EMAP II. Experiments were performed in endothelium-intact rings, endothelium-denuded rings, and in the presence of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME). Pulmonary artery rings were then subjected to quantitative PCR analysis for inducible NOS (iNOS) mRNA. EMAPII caused a maximal vasodilation of 251 ± 30.7 mg in endothelium-intact PA. EMAP II caused no vasodilation in endothelium-denuded and L-NAME-treated PA (20 ± 14.0 mg and 17.5 ± 7.5 mg, respectively, P < 0.001 vs. endothelium intact). In addition to its vasoactive properties, EMAP II increased PA iNOS mRNA twofold compared with controls. These results demonstrate that 1) EMAP II causes PA vasodilation; 2) EMAP II-mediated PA vasodilation is endothelium dependent and NOS dependent; and 3) EMAP II upregulates iNOS mRNA expression in PA. This report constitutes the first demonstration of EMAP IPs effects on the pulmonary artery, its mechanism of action, and represents the identification of the first proinflammatory cytokine to cause PA vasodilation.

Original languageEnglish
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume287
Issue number4 56-4
DOIs
StatePublished - Oct 2004

Fingerprint

Vasodilation
Pulmonary Artery
Cytokines
Endothelium
NG-Nitroarginine Methyl Ester
Messenger RNA
small inducible cytokine subfamily E, member 1
Steel
Phenylephrine
Transducers
Baths
Sprague Dawley Rats
Monocytes
Up-Regulation
Polymerase Chain Reaction
Peptides

Keywords

  • Acute lung injury
  • Apoptosis
  • Endothelium
  • Hypoxia
  • Inflammation

ASJC Scopus subject areas

  • Physiology

Cite this

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title = "Endothelial monocyte-activating polypeptide II causes NOS-dependent pulmonary artery vasodilation: A novel effect for a proinflammatory cytokine",
abstract = "Endothelial monocyte-activating polypeptide (EMAP) II is a novel proinflammatory cytokine that is released from apoptotic and hypoxic cells. The purpose of this study was to determine the effect of EMAP II on the pulmonary artery (PA) and to characterize its mechanism of action. To study this, isolated PA rings from adult male Sprague-Dawley rats were suspended on steel hooks connected to force transducers and immersed in 37°C organ baths containing modified Krebs-Henseleit solution. After equilibration, force displacement of phenylephrine-preconstricted PA was measured in response to EMAP II. Experiments were performed in endothelium-intact rings, endothelium-denuded rings, and in the presence of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME). Pulmonary artery rings were then subjected to quantitative PCR analysis for inducible NOS (iNOS) mRNA. EMAPII caused a maximal vasodilation of 251 ± 30.7 mg in endothelium-intact PA. EMAP II caused no vasodilation in endothelium-denuded and L-NAME-treated PA (20 ± 14.0 mg and 17.5 ± 7.5 mg, respectively, P < 0.001 vs. endothelium intact). In addition to its vasoactive properties, EMAP II increased PA iNOS mRNA twofold compared with controls. These results demonstrate that 1) EMAP II causes PA vasodilation; 2) EMAP II-mediated PA vasodilation is endothelium dependent and NOS dependent; and 3) EMAP II upregulates iNOS mRNA expression in PA. This report constitutes the first demonstration of EMAP IPs effects on the pulmonary artery, its mechanism of action, and represents the identification of the first proinflammatory cytokine to cause PA vasodilation.",
keywords = "Acute lung injury, Apoptosis, Endothelium, Hypoxia, Inflammation",
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T1 - Endothelial monocyte-activating polypeptide II causes NOS-dependent pulmonary artery vasodilation

T2 - A novel effect for a proinflammatory cytokine

AU - Tsai, Ben M.

AU - Wang, Meijing

AU - Clauss, Matthias

AU - Sun, Peichuan

AU - Meldrum, Daniel R.

PY - 2004/10

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N2 - Endothelial monocyte-activating polypeptide (EMAP) II is a novel proinflammatory cytokine that is released from apoptotic and hypoxic cells. The purpose of this study was to determine the effect of EMAP II on the pulmonary artery (PA) and to characterize its mechanism of action. To study this, isolated PA rings from adult male Sprague-Dawley rats were suspended on steel hooks connected to force transducers and immersed in 37°C organ baths containing modified Krebs-Henseleit solution. After equilibration, force displacement of phenylephrine-preconstricted PA was measured in response to EMAP II. Experiments were performed in endothelium-intact rings, endothelium-denuded rings, and in the presence of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME). Pulmonary artery rings were then subjected to quantitative PCR analysis for inducible NOS (iNOS) mRNA. EMAPII caused a maximal vasodilation of 251 ± 30.7 mg in endothelium-intact PA. EMAP II caused no vasodilation in endothelium-denuded and L-NAME-treated PA (20 ± 14.0 mg and 17.5 ± 7.5 mg, respectively, P < 0.001 vs. endothelium intact). In addition to its vasoactive properties, EMAP II increased PA iNOS mRNA twofold compared with controls. These results demonstrate that 1) EMAP II causes PA vasodilation; 2) EMAP II-mediated PA vasodilation is endothelium dependent and NOS dependent; and 3) EMAP II upregulates iNOS mRNA expression in PA. This report constitutes the first demonstration of EMAP IPs effects on the pulmonary artery, its mechanism of action, and represents the identification of the first proinflammatory cytokine to cause PA vasodilation.

AB - Endothelial monocyte-activating polypeptide (EMAP) II is a novel proinflammatory cytokine that is released from apoptotic and hypoxic cells. The purpose of this study was to determine the effect of EMAP II on the pulmonary artery (PA) and to characterize its mechanism of action. To study this, isolated PA rings from adult male Sprague-Dawley rats were suspended on steel hooks connected to force transducers and immersed in 37°C organ baths containing modified Krebs-Henseleit solution. After equilibration, force displacement of phenylephrine-preconstricted PA was measured in response to EMAP II. Experiments were performed in endothelium-intact rings, endothelium-denuded rings, and in the presence of the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME). Pulmonary artery rings were then subjected to quantitative PCR analysis for inducible NOS (iNOS) mRNA. EMAPII caused a maximal vasodilation of 251 ± 30.7 mg in endothelium-intact PA. EMAP II caused no vasodilation in endothelium-denuded and L-NAME-treated PA (20 ± 14.0 mg and 17.5 ± 7.5 mg, respectively, P < 0.001 vs. endothelium intact). In addition to its vasoactive properties, EMAP II increased PA iNOS mRNA twofold compared with controls. These results demonstrate that 1) EMAP II causes PA vasodilation; 2) EMAP II-mediated PA vasodilation is endothelium dependent and NOS dependent; and 3) EMAP II upregulates iNOS mRNA expression in PA. This report constitutes the first demonstration of EMAP IPs effects on the pulmonary artery, its mechanism of action, and represents the identification of the first proinflammatory cytokine to cause PA vasodilation.

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KW - Apoptosis

KW - Endothelium

KW - Hypoxia

KW - Inflammation

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