doi: 10.1161/CIRCRESAHA.107.162511
© 2007 American Heart Association, Inc.
Review |
Phosphodiesterase Type 5
Expanding Roles in Cardiovascular Regulation
From the Division of Cardiology (D.A.K., H.C.C.), Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Md; and the Department of Pharmacology (J.A.B.), University of Washington, Seattle.
Correspondence to David A. Kass, MD, Ross 835, 720 Rutland Avenue, Johns Hopkins Medical Institutions, Baltimore, MD 21205. E-mail dkass{at}jhmi.edu
This Review is part of a thematic series on Phosphodiesterases, which includes the following articles:
Compartmentation of Cyclic Nucleotide Signaling in the Heart: The Role of Cyclic Nucleotide Phosphodiesterases
Overview of PDEs and their Regulation
Regulation of Phosphodiesterase 3 (PDE3) and Inducible cAMP Early Repressor in the Heart
cAMP Specific Phosphodiesterase-4 Enzymes in the Cardiovascular System: A Molecular Toolbox for Generating
Compartmentalized cAMP Signalling
cAMP and cGMP Signaling Cross-Talk: Role of Phosphodiesterases and Implications for Cardiac Pathophysiology
Phosphodiesterase Type 5: Expanding Roles in Cardiovascular Regulation
David A. Kass Editor
Phosphodiesterase type 5A (PDE5A) selectively hydrolyzes cyclic GMP. Inhibitors of PDE5A such as sildenafil are widely used to treat erectile dysfunction, but growing evidence supports important roles for the enzyme in both the vasculature and heart. In disorders such as cardiac failure, PDE5A upregulation may contribute to a decline in cGMP and protein kinase G signaling, exacerbating dysfunction. PDE5A plays an important role in the pulmonary vasculature where its inhibition benefits patients with pulmonary hypertension. In the heart, PDE5A signaling appears compartmentalized, and its inhibition is cardioprotective against ischemia-reperfusion and antracycline toxicity, blunts acute adrenergic contractile stimulation, and can suppress chronic hypertrophy and dysfunction attributable to pressure-overload. In this review, we discuss the molecular biology, pharmacology, and physiology of PDE5A, mechanisms of vascular and cardiac regulation, and recent evidence supporting the utility of selective PDE5A inhibition for the treatment of cardiovascular disorders.
Key Words: blood vessels • cardiac myocytes • cardiovascular physiology • phosphodiesterase type 5 inhibitor • pressure overload • protein kinase G • reperfusion injury
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