Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress
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Date
2013-07Author
Bivalacqua, Trinity J.
Musicki, Biljana
Hsu, Lewis L.
Berkowitz, Dan E.
Champion, Hunter C.
Burnett, Arthur L.
Publisher
PLoS OneMetadata
Show full item recordAbstract
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.