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Combination of nonspecific PDE inhibitors with inhaled prostacyclin in experimental pulmonary hypertension
- Source :
- Scopus-Elsevier
- Publication Year :
- 2001
- Publisher :
- American Physiological Society, 2001.
-
Abstract
- Inhalation of aerosolized prostacyclin (PGI2) exerts selective pulmonary vasodilation, but its effect is rapidly lost after termination of nebulization. Amplification of the vasodilatory response to inhaled PGI2 might be achieved by phosphodiesterase (PDE) inhibitors to stabilize its second messenger, cAMP. We established stable pulmonary hypertension in perfused rabbit lungs by continuous infusion of U-46619. Short-term (10-min) aerosolization maneuvers of PGI2 effected a rapid, moderate decrease in pulmonary arterial pressure, with post-PGI2 vasorelaxation being lost within 10–15 min, accompanied by a marginal reduction in shunt flow. Preceding administration of subthreshold doses of the PDE inhibitors theophylline, dipyridamole, and pentoxifylline via the intravascular or inhalational route, which per se did not influence pulmonary hemodynamics, caused more than doubling of the immediate pulmonary arterial pressure drop in response to PGI2 and marked prolongation of the post-PGI2 vasorelaxation to >60 min (all PDE inhibitors via both routes of application). This was accompanied by a reduction in shunt flow in the case of aerosolized theophylline (27.5%), pentoxifylline (30.5%), and dipyridamole (33.4%). Coaerosolization of PGI2 and PDE inhibitors may be considered as a therapeutic strategy in pulmonary hypertension.
- Subjects :
- Pulmonary and Respiratory Medicine
Phosphodiesterase Inhibitors
Physiology
Hypertension, Pulmonary
Vasodilation
Prostacyclin
Pharmacology
Theophylline
Physiology (medical)
medicine.artery
Administration, Inhalation
Cyclic AMP
Pressure
Ventilation-Perfusion Ratio
medicine
Animals
Vasoconstrictor Agents
Pentoxifylline
Antihypertensive Agents
Dose-Response Relationship, Drug
Inhalation
Pulmonary Gas Exchange
business.industry
Nebulizers and Vaporizers
Dipyridamole
Cell Biology
medicine.disease
Epoprostenol
Pulmonary hypertension
medicine.anatomical_structure
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Anesthesia
Circulatory system
Pulmonary artery
Drug Therapy, Combination
lipids (amino acids, peptides, and proteins)
Rabbits
business
medicine.drug
Blood vessel
Subjects
Details
- ISSN :
- 15221504 and 10400605
- Volume :
- 281
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Lung Cellular and Molecular Physiology
- Accession number :
- edsair.doi.dedup.....9bfa8b47fd641830926e796a27a4384a