Cardiovascular diseases (CVD) are considered a major health problem worldwide, being the main
cause of mortality in developing and developed countries. Endothelial dysfunction, characterized by a decline in
nitric oxide production and/or bioavailability, increased oxidative stress, decreased prostacyclin levels, and a
reduction of endothelium-derived hyperpolarizing factor is considered an important prognostic indicator of various
CVD. Changes in cyclic nucleotides production and/ or signalling, such as guanosine 3', 5'-monophosphate
(cGMP) and adenosine 3', 5'-monophosphate (cAMP), also accompany many vascular disorders that course with
altered endothelial function. Phosphodiesterases (PDE) are metallophosphohydrolases that catalyse cAMP and
cGMP hydrolysis, thereby terminating the cyclic nucleotide-dependent signalling. The development of drugs that
selectively block the activity of specific PDE families remains of great interest to the research, clinical and pharmaceutical
industries. In the present review, we will discuss the effects of PDE inhibitors on CVD related to
altered endothelial function, such as atherosclerosis, diabetes mellitus, arterial hypertension, stroke, aging and
cirrhosis. Multiple evidences suggest that PDEs inhibition represents an attractive medical approach for the
treatment of endothelial dysfunction-related diseases. Selective PDE inhibitors, especially PDE3 and PDE5 inhibitors
are proposed to increase vascular NO levels by increasing antioxidant status or endothelial nitric oxide
synthase expression and activation and to improve the morphological architecture of the endothelial surface.
Thereby, selective PDE inhibitors can improve the endothelial function in various CVD, increasing the evidence
that these drugs are potential treatment strategies for vascular dysfunction and reinforcing their potential role as
an adjuvant in the pharmacotherapy of CVD.
FEATURES OF NITRIC OXIDE METABOLISM AND RISK OF DEVELOPING ENDOTHELIAL DYSFUNCTION IN CHILDREN WITH e-NOS GENE 4a/4b POLYMORPHISM UNDER LONG/TERM ENTERING 137Cs TO BODY
