Abstract
Phosphodiesterases (PDE) are a class of proteins whose most relevant biological activity concerns the modulation of intracellular levels of cyclic nucleotides, e.g., cGMP and cAMP. PDE isoenzyme 5 (PDE5) is specifically involved in cGMP inactivation in the smooth muscle cell. Chemical inhibition of PDE5 by sildenafil, tadalafil or vardenafil recently became a valid therapeutic option aimed at overexpressing the molecular pathway originated from nitric oxide and expressed via increased cell cGMP availability. Based on the optimal tolerability and proven efficacy in various human disorders, EMEA and FDA have approved PDE5 inhibition as an efficient therapy in some cardiovascular, pulmonary and vascular diseases. More specifically, PDE5 inhibition appears successful for the treatment of idiopathic arterial pulmonary hypertension. Furthermore, PDE5 inhibition resulted in important protective effects in the myocardium, i.e., antyhypertrophic and antiapoptic, as well as vascular functions, i.e., increased tolerance to ischemia/reperfusion injury and improved endothelial function, thereby implying a potential usefulness in the treatment of patients with heart failure and coronary artery disease. Evidence currently available for considering PDE5-inhibition an additional opportunity in the treatment of common cardiopulmonary disorders is here provided.
Keywords: Nitric oxide, cGMP, sildenafil, vardenafil, tadalafil, pulmonary hypertension, heart failure
Current Medicinal Chemistry
Title: The Role of PDE5-Inhibitors in Cardiopulmonary Disorders: From Basic Evidence to Clinical Development
Volume: 14 Issue: 20
Author(s): Marco Guazzi and Michele Samaja
Affiliation:
Keywords: Nitric oxide, cGMP, sildenafil, vardenafil, tadalafil, pulmonary hypertension, heart failure
Abstract: Phosphodiesterases (PDE) are a class of proteins whose most relevant biological activity concerns the modulation of intracellular levels of cyclic nucleotides, e.g., cGMP and cAMP. PDE isoenzyme 5 (PDE5) is specifically involved in cGMP inactivation in the smooth muscle cell. Chemical inhibition of PDE5 by sildenafil, tadalafil or vardenafil recently became a valid therapeutic option aimed at overexpressing the molecular pathway originated from nitric oxide and expressed via increased cell cGMP availability. Based on the optimal tolerability and proven efficacy in various human disorders, EMEA and FDA have approved PDE5 inhibition as an efficient therapy in some cardiovascular, pulmonary and vascular diseases. More specifically, PDE5 inhibition appears successful for the treatment of idiopathic arterial pulmonary hypertension. Furthermore, PDE5 inhibition resulted in important protective effects in the myocardium, i.e., antyhypertrophic and antiapoptic, as well as vascular functions, i.e., increased tolerance to ischemia/reperfusion injury and improved endothelial function, thereby implying a potential usefulness in the treatment of patients with heart failure and coronary artery disease. Evidence currently available for considering PDE5-inhibition an additional opportunity in the treatment of common cardiopulmonary disorders is here provided.
Export Options
About this article
Cite this article as:
Marco Guazzi and Michele Samaja , The Role of PDE5-Inhibitors in Cardiopulmonary Disorders: From Basic Evidence to Clinical Development, Current Medicinal Chemistry 2007; 14 (20) . https://dx.doi.org/10.2174/092986707781389619
DOI https://dx.doi.org/10.2174/092986707781389619 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Cerebral White Matter Injuries Following a Hypoxic/Ischemic Insult During the Perinatal Period: Pathophysiology, Prognostic Factors, and Future Strategy of Treatment Approach. A Minireview
Current Pharmaceutical Design Energetic Metabolic Roles in Pulmonary Arterial Hypertension and Right Ventricular Remodeling
Current Pharmaceutical Design Selenium in the Therapy of Neurological Diseases. Where is it Going?
Current Neuropharmacology Anti-Diabetic Effects of Isolated Lipids from Natural Sources through Modulation of Angiogenesis
Current Molecular Pharmacology Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease
Current Topics in Medicinal Chemistry Nanocapsulated Ascorbic Acid in Combating Cerebral Ischemia Reperfusion- Induced Oxidative Injury in Rat Brain
Current Alzheimer Research Nitric Oxide as a Marker for Levo-Thyroxine Therapy in Subclinical Hypothyroid Patients
Current Vascular Pharmacology Mechanisms Underlying Beneficial Health Effects of Tea Catechins to Improve Insulin Resistance and Endothelial Dysfunction
Endocrine, Metabolic & Immune Disorders - Drug Targets Water and Ion Channels: Crucial in the Initiation and Progression of Apoptosis in Central Nervous System?
Current Neuropharmacology Concepts of Egr-1 Activation – A Hub for Signal Transduction Cascades
Current Signal Transduction Therapy Targeting STAT1 in Both Cancer and Insulin Resistance Diseases
Current Protein & Peptide Science Pharmacological Interventions and Rehabilitation Approach for Enhancing Brain Self-repair and Stroke Recovery
Current Neuropharmacology Caveolin-1: A Promising Therapeutic Target for Diverse Diseases
Current Molecular Pharmacology Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Mechanical Intervention for Acute Myocardial Infarction
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Potential Medications or Compounds Acting on Toll-like Receptors in Cerebral Ischemia
Current Neuropharmacology Tissue Plasminogen Activator (tPA) and Matrix Metalloproteinases in the Pathogenesis of Stroke: Therapeutic Strategies
CNS & Neurological Disorders - Drug Targets Autophagy in Diabetic Retinopathy
Current Neuropharmacology Pharmacological Approach of No-Reflow Phenomenon Related with Percutaneous Coronary Interventions
Cardiovascular & Hematological Agents in Medicinal Chemistry Drug-Induced Hypothermia in Stroke Models: Does it Always Protect?
CNS & Neurological Disorders - Drug Targets Cytokine Gene Polymorphism in Heart Transplantation: A Review
Current Genomics