Effect of selective phosphodiesterase inhibitors on response of ovine pulmonary arteries to prostaglandin E2.

Détails

ID Serval
serval:BIB_B4EF4D2CA33F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Effect of selective phosphodiesterase inhibitors on response of ovine pulmonary arteries to prostaglandin E2.
Périodique
Journal of Applied Physiology
Auteur⸱e⸱s
Gao Y., Tolsa J.F., Shen H., Raj J.U.
ISSN
8750-7587
Statut éditorial
Publié
Date de publication
1998
Peer-reviewed
Oui
Volume
84
Numéro
1
Pages
13-18
Langue
anglais
Notes
Publication types: In Vitro ; Journal Article
Résumé
Several adenosine 3',5'-cyclic monophosphate (cAMP)-hydrolyzing phosphodiesterase isozymes are present in the pulmonary vasculature. The present study was designed to determine the effect of selective inhibitors of phosphodiesterase subtypes on prostaglandin E2 (PGE2)-induced relaxation of isolated fourth-generation pulmonary arteries of newborn lambs. PGE2 and forskolin caused pulmonary arteries to relax and induced an increase in the intracellular cAMP content in the vessels. The relaxation and change in cAMP content were augmented by milrinone and rolipram, inhibitors of phosphodiesterase type 3 (PDE3) and type 4 (PDE4), respectively. The augmentation in relaxation and the increase in cAMP content caused by milrinone plus rolipram was greater than the sum of the responses caused by either of the inhibitors alone. 8-Methoxymethyl-1-methyl-3-(2-methylpropyl)xanthine, an inhibitor of phosphodiesterase type 1, had no effect on relaxation and change in cAMP induced by PGE2 and forskolin. Acetylcholine alone had no effect on cAMP content in the vessels but augmented the relaxation and the increase in cAMP induced by PGE2 and forskolin in arteries with endothelium. This effect was not observed in arteries without endothelium or in arteries with endothelium treated with NG-nitro-L-arginine. These results suggest that PDE3 and PDE4 are the primary enzymes hydrolyzing cAMP of pulmonary arteries of newborn lambs and that an inhibition of both PDE3 and PDE4 would result in a greater effect than that caused by inhibition of either one of the subtype isozymes alone. Furthermore, endothelium-derived nitric oxide may enhance cAMP-mediated relaxation by inhibition of PDE3.
Mots-clé
Animals, Animals, Newborn, Cyclic AMP/metabolism, Cyclic GMP/metabolism, Dinoprostone/pharmacology, Female, Male, Muscle, Smooth, Vascular/drug effects, Muscle, Smooth, Vascular/metabolism, Phosphodiesterase Inhibitors/pharmacology, Pulmonary Artery/drug effects, Pulmonary Artery/metabolism, Sheep
Pubmed
Web of science
Création de la notice
28/01/2008 14:52
Dernière modification de la notice
20/08/2019 16:23
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