Document Detail


Role of phosphodiesterases in adult-onset pulmonary arterial hypertension.
MedLine Citation:
PMID:  21695645     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pulmonary arterial hypertension (PAH) is characterized by increased mean pulmonary artery pressure (mPAP) due to vasoconstriction and structural changes in the small pulmonary arteries (PAs); proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the remodeling. The abnormal pathophysiology in the pulmonary vasculature relates to decreased cyclic nucleotide levels in PASMCs. Phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP, thereby PDE inhibitors are effective in vasodilating the PA and decreasing PASMC proliferation. Experimental studies support the use of PDE3, PDE5, and PDE1 inhibitors in PAH. PDE5 inhibitors such as sildenafil are clinically approved to treat different forms of PAH and lower mPAP, increase functional capacity, and decrease right ventricular hypertrophy, without decreasing systemic arterial pressure. New evidence suggests that the combination of PDE inhibitors with other therapies for PAH may be beneficial in treating the disease. Furthermore, inhibiting PDEs in the heart and the inflammatory cells that infiltrate the PA may offer new targets to reduce right ventricular hypertrophy and inhibit inflammation that is associated with and contributes to the development of PAH. This chapter summarizes the advances in the area and the future of PDEs in PAH.
Authors:
F Murray; M R Maclean; P A Insel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Handbook of experimental pharmacology     Volume:  -     ISSN:  0171-2004     ISO Abbreviation:  Handb Exp Pharmacol     Publication Date:  2011  
Date Detail:
Created Date:  2011-06-22     Completed Date:  2011-09-20     Revised Date:  2012-06-11    
Medline Journal Info:
Nlm Unique ID:  7902231     Medline TA:  Handb Exp Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  279-305     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Department of Medicine, BSB 3073, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0636, USA. fmurray@ucsd.edu
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MeSH Terms
Descriptor/Qualifier:
Cyclic Nucleotide Phosphodiesterases, Type 1 / physiology
Humans
Hypertension, Pulmonary / drug therapy,  etiology*
Nucleotides, Cyclic / physiology
Phosphodiesterase 3 Inhibitors / therapeutic use
Phosphodiesterase 5 Inhibitors / therapeutic use
Phosphodiesterase Inhibitors / therapeutic use
Phosphoric Diester Hydrolases / physiology*
Grant Support
ID/Acronym/Agency:
K99HL091061/HL/NHLBI NIH HHS; R00 HL091061/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Nucleotides, Cyclic; 0/Phosphodiesterase 3 Inhibitors; 0/Phosphodiesterase 5 Inhibitors; 0/Phosphodiesterase Inhibitors; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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