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Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress
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Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress
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Journal Article
Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress
2013
Overview
Sildenafil citrate revolutionized the practice of sexual medicine upon its federal regulatory agency approval approximately 15 years ago as the prototypical phosphodiesterase type 5 inhibitor indicated for the treatment of male erectile dysfunction. We now provide scientific support for its alternative use in the management of priapism, a clinical disorder of prolonged and uncontrolled penile erection. Sildenafil administered continuously to sickle cell mice, which show a priapism phenotype, reverses oxidative/nitrosative stress effects in the penis, mainly via reversion of uncoupled endothelial nitric oxide synthase to the functional coupled state of the enzyme, which in turn corrects aberrant signaling and function of the nitric oxide/cyclic GMP/protein kinase G/phosphodiesterase type 5 cascade. Priapism tendencies in these mice are reverted partially toward normal neurostimulated erection frequencies and durations after sildenafil treatment in association with normalized cyclic GMP concentration, protein kinase G activity and phosphodiesterase type 5 activity in the penis. Thus, sildenafil exerts pleiotropic effects in the penis that extend to diverse erection disorders.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Anemia, Sickle Cell - complications
/ Anemia, Sickle Cell - genetics
/ Animals
/ Biology
/ Complications and side effects
/ Cyclic GMP-Dependent Protein Kinases - metabolism
/ Cyclic Nucleotide Phosphodiesterases, Type 5 - metabolism
/ Erection
/ Humans
/ Kinases
/ Male
/ Medicine
/ Mice
/ Nitric Oxide Synthase Type III - metabolism
/ Oxidative Stress - drug effects
/ Penis
/ Phosphodiesterase 5 Inhibitors - pharmacology
/ Priapism
/ Priapism - prevention & control
/ Proteins
/ Reactive Oxygen Species - metabolism
/ Rodents
/ Signal Transduction - drug effects
/ Studies
