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 language | English (US) |
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Pages (from-to) | 131-138 |
Number of pages | 8 |
Journal | Acta Pharmacologica Sinica |
Volume | 21 |
Issue number | 2 |
State | Published - Feb 2000 |
Keywords
- Cyclic AMP
- Cyclic GMP
- Epoprostenol
- Nitric acid
- Phosphoric diester hydrolases
- Pulmonary artery
- Vascular endothelium
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)