Prostacyclin-induced relaxations of small porcine pulmonary arteries are enhanced by the basal release of endothelium-derived nitric oxide through an effect on cyclic GMP-inhibited-cyclic AMP phosphodiesterase

Thomas M. Zellers, Yi Qun Wu, Jennifer McCormick, Paul M. Vanhoutte

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9 Citations (Scopus)

Abstract

AIM: To study the interactions between prostacyclin and endothelium- derived nitric oxide in porcine pulmonary arteries. METHODS: Rings of 5th order of porcine pulmonary arteries were studied in vitro for the measurement of tension and the content in cyclic nucleotides. RESULTS: Prostacyclin, given exogenously, caused endothelium-potentiated relaxations (inhibition of phenylephrine contraction) that were inhibited by the inhibitors of the L- arginine nitric oxide pathway, oxyhemoglobin and N(ω)-nitro-L-arginine. These inhibitors did not affect the tension in rings without endothelium. Cyclic GMP-concentrations were not increased above basal concentrations in the presence of prostacyclin. Increases were seen with acetylcholine and sodium nitroprusside. Prostacyclin-stimulated cyclic AMP concentrations did not reach statistical significance compared to controls. The addition of 8- bromo-cyclic GMP to prostacyclin, however, increased the cyclic AMP content. The nitric oxide synthase inhibitor, nitro-L-arginine (NLA), reduced the prostacyclin-stimulated cyclic AMP content to basal level. Inhibition of cyclic GMP-inhibited cyclic AMP phosphodiesterase by 8-bromo-cyclic GMP or amrinone (a specific inhibitor of this enzyme) potentiated the prostacyclin- induced relaxations in rings without endothelium to a magnitude similar to that observed in rings with endothelium. CONCLUSION: These data suggest that the augmentation by the endothelium of the prostacyclin-induced relaxation of porcine pulmonary arteries is secondary to the inhibition of cyclic GMP- inhibited cyclic AMP phosphodiesterase by basally released endothelium- derived nitric oxide.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalActa Pharmacologica Sinica
Volume21
Issue number2
StatePublished - Feb 2000

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Cyclic GMP
Phosphoric Diester Hydrolases
Epoprostenol
Cyclic AMP
Pulmonary Artery
Nitric Oxide
Swine
Endothelium
Arginine
Amrinone
Oxyhemoglobins
Cyclic Nucleotides
Nitroprusside
Enzyme Inhibitors
Phenylephrine
Nitric Oxide Synthase
Acetylcholine

Keywords

  • Cyclic AMP
  • Cyclic GMP
  • Epoprostenol
  • Nitric acid
  • Phosphoric diester hydrolases
  • Pulmonary artery
  • Vascular endothelium

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmacology

Cite this

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title = "Prostacyclin-induced relaxations of small porcine pulmonary arteries are enhanced by the basal release of endothelium-derived nitric oxide through an effect on cyclic GMP-inhibited-cyclic AMP phosphodiesterase",
abstract = "AIM: To study the interactions between prostacyclin and endothelium- derived nitric oxide in porcine pulmonary arteries. METHODS: Rings of 5th order of porcine pulmonary arteries were studied in vitro for the measurement of tension and the content in cyclic nucleotides. RESULTS: Prostacyclin, given exogenously, caused endothelium-potentiated relaxations (inhibition of phenylephrine contraction) that were inhibited by the inhibitors of the L- arginine nitric oxide pathway, oxyhemoglobin and N(ω)-nitro-L-arginine. These inhibitors did not affect the tension in rings without endothelium. Cyclic GMP-concentrations were not increased above basal concentrations in the presence of prostacyclin. Increases were seen with acetylcholine and sodium nitroprusside. Prostacyclin-stimulated cyclic AMP concentrations did not reach statistical significance compared to controls. The addition of 8- bromo-cyclic GMP to prostacyclin, however, increased the cyclic AMP content. The nitric oxide synthase inhibitor, nitro-L-arginine (NLA), reduced the prostacyclin-stimulated cyclic AMP content to basal level. Inhibition of cyclic GMP-inhibited cyclic AMP phosphodiesterase by 8-bromo-cyclic GMP or amrinone (a specific inhibitor of this enzyme) potentiated the prostacyclin- induced relaxations in rings without endothelium to a magnitude similar to that observed in rings with endothelium. CONCLUSION: These data suggest that the augmentation by the endothelium of the prostacyclin-induced relaxation of porcine pulmonary arteries is secondary to the inhibition of cyclic GMP- inhibited cyclic AMP phosphodiesterase by basally released endothelium- derived nitric oxide.",
keywords = "Cyclic AMP, Cyclic GMP, Epoprostenol, Nitric acid, Phosphoric diester hydrolases, Pulmonary artery, Vascular endothelium",
author = "Zellers, {Thomas M.} and Wu, {Yi Qun} and Jennifer McCormick and Vanhoutte, {Paul M.}",
year = "2000",
month = "2",
language = "English (US)",
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pages = "131--138",
journal = "Zhongguo yao li xue bao = Acta pharmacologica Sinica",
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TY - JOUR

T1 - Prostacyclin-induced relaxations of small porcine pulmonary arteries are enhanced by the basal release of endothelium-derived nitric oxide through an effect on cyclic GMP-inhibited-cyclic AMP phosphodiesterase

AU - Zellers, Thomas M.

AU - Wu, Yi Qun

AU - McCormick, Jennifer

AU - Vanhoutte, Paul M.

PY - 2000/2

Y1 - 2000/2

N2 - AIM: To study the interactions between prostacyclin and endothelium- derived nitric oxide in porcine pulmonary arteries. METHODS: Rings of 5th order of porcine pulmonary arteries were studied in vitro for the measurement of tension and the content in cyclic nucleotides. RESULTS: Prostacyclin, given exogenously, caused endothelium-potentiated relaxations (inhibition of phenylephrine contraction) that were inhibited by the inhibitors of the L- arginine nitric oxide pathway, oxyhemoglobin and N(ω)-nitro-L-arginine. These inhibitors did not affect the tension in rings without endothelium. Cyclic GMP-concentrations were not increased above basal concentrations in the presence of prostacyclin. Increases were seen with acetylcholine and sodium nitroprusside. Prostacyclin-stimulated cyclic AMP concentrations did not reach statistical significance compared to controls. The addition of 8- bromo-cyclic GMP to prostacyclin, however, increased the cyclic AMP content. The nitric oxide synthase inhibitor, nitro-L-arginine (NLA), reduced the prostacyclin-stimulated cyclic AMP content to basal level. Inhibition of cyclic GMP-inhibited cyclic AMP phosphodiesterase by 8-bromo-cyclic GMP or amrinone (a specific inhibitor of this enzyme) potentiated the prostacyclin- induced relaxations in rings without endothelium to a magnitude similar to that observed in rings with endothelium. CONCLUSION: These data suggest that the augmentation by the endothelium of the prostacyclin-induced relaxation of porcine pulmonary arteries is secondary to the inhibition of cyclic GMP- inhibited cyclic AMP phosphodiesterase by basally released endothelium- derived nitric oxide.

AB - AIM: To study the interactions between prostacyclin and endothelium- derived nitric oxide in porcine pulmonary arteries. METHODS: Rings of 5th order of porcine pulmonary arteries were studied in vitro for the measurement of tension and the content in cyclic nucleotides. RESULTS: Prostacyclin, given exogenously, caused endothelium-potentiated relaxations (inhibition of phenylephrine contraction) that were inhibited by the inhibitors of the L- arginine nitric oxide pathway, oxyhemoglobin and N(ω)-nitro-L-arginine. These inhibitors did not affect the tension in rings without endothelium. Cyclic GMP-concentrations were not increased above basal concentrations in the presence of prostacyclin. Increases were seen with acetylcholine and sodium nitroprusside. Prostacyclin-stimulated cyclic AMP concentrations did not reach statistical significance compared to controls. The addition of 8- bromo-cyclic GMP to prostacyclin, however, increased the cyclic AMP content. The nitric oxide synthase inhibitor, nitro-L-arginine (NLA), reduced the prostacyclin-stimulated cyclic AMP content to basal level. Inhibition of cyclic GMP-inhibited cyclic AMP phosphodiesterase by 8-bromo-cyclic GMP or amrinone (a specific inhibitor of this enzyme) potentiated the prostacyclin- induced relaxations in rings without endothelium to a magnitude similar to that observed in rings with endothelium. CONCLUSION: These data suggest that the augmentation by the endothelium of the prostacyclin-induced relaxation of porcine pulmonary arteries is secondary to the inhibition of cyclic GMP- inhibited cyclic AMP phosphodiesterase by basally released endothelium- derived nitric oxide.

KW - Cyclic AMP

KW - Cyclic GMP

KW - Epoprostenol

KW - Nitric acid

KW - Phosphoric diester hydrolases

KW - Pulmonary artery

KW - Vascular endothelium

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JO - Zhongguo yao li xue bao = Acta pharmacologica Sinica

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