Related Experiment Video
Updated: Aug 4, 2026
09:23
Isolation of Microvascular Endothelial Tubes from Mouse Resistance Arteries
Published on: November 25, 2013
Cyclic nucleotide phosphodiesterases and vascular smooth muscle
1Department of Pharmacology and Therapeutics, University of South Florida, College of Medicine, Tampa 33612-4799, USA.
Annual Review of Pharmacology and Toxicology
|January 1, 1996
Summary
Phosphodiesterase (PDE) inhibitors, particularly PDE3 isoform inhibitors, promote vascular relaxation and possess antiplatelet activities. Selective PDE inhibitors may offer new therapeutic strategies for cardiovascular diseases and restenosis.
Area of Science:
- Biochemistry
- Pharmacology
- Cardiovascular Biology
Background:
- Over 30 phosphodiesterase (PDE) enzymes exist in mammals, classified into seven families.
- Specific inhibitors are available for at least five PDE families, enabling targeted research.
- PDEs in vascular smooth muscle can be functionally classified by substrate, regulation, and inhibitor sensitivity.
Purpose of the Study:
- To describe the functional classification of phosphodiesterases (PDEs) in vascular smooth muscle.
- To explore the therapeutic potential of PDE inhibitors in cardiovascular diseases.
- To investigate the role of selective PDE inhibitors in modulating vascular smooth muscle phenotype.
Main Methods:
- Functional classification of PDEs based on substrate specificity, regulatory properties, and inhibitor sensitivity.
- Assessment of PDE inhibitor effects on vascular smooth muscle, including endothelium-denuded preparations.
- Evaluation of PDE inhibitors' impact on vascular smooth muscle cell phenotype in culture.
Main Results:
- Inhibition of vascular smooth muscle PDEs, especially PDE3, induces relaxation, particularly in pre-contracted muscle.
- PDE3 inhibitors exhibit cardiotonic, antiplatelet, and thrombolytic effects, suggesting cardiovascular benefits.
- Selective PDE inhibitors can shift vascular smooth muscle cells from a synthetic to a contractile phenotype, potentially preventing restenosis.
Conclusions:
- PDE inhibitors, particularly PDE3-selective agents, hold significant therapeutic promise for cardiovascular conditions.
- Targeting specific PDE isoforms may offer novel treatments for restenosis after angioplasty.
- Advancements in targeted delivery of PDE inhibitors could unlock new therapeutic applications in cardiovascular medicine.
More Related Videos
Related Concept Videos
01:15Amplifying Signals via Second Messengers
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
01:28Nitric Oxide Signaling Pathway
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
01:25Smooth Muscle Contraction
Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
01:18Antihypertensive Drugs: Action of Calcium Channel Blockers
Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
01:16Vascular Spasm
The vascular phase, also known as vasospasm, is the initial stage of hemostasis, crucial for preventing excessive bleeding when a blood vessel is injured. After a vessel is cut, nerves in the damaged area trigger pain and other sensory impulses. Simultaneously, the smooth muscles in the vessel wall contract, resulting in a vascular spasm. This contraction reduces the vessel's diameter at the injury site, slowing or stopping blood loss through the vessel wall. Vascular spasms typically last for...