Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress

Bivalacqua, TJ and Musicki, B and Hsu, LL and Berkowitz, DE and Champion, HC and Burnett, AL (2013) Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress. PLoS ONE, 8 (7).

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Abstract

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. © 2013 Bivalacqua et al.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Bivalacqua, TJ Musicki, B Hsu, LL Berkowitz, DE Champion, HC Burnett, AL
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Koul, Hari UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	2 July 2013
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	8
Number:	7
DOI or Unique Handle:	10.1371/journal.pone.0068028
Schools and Programs:	School of Medicine > Medicine
Refereed:	Yes
Other ID:	NLM PMC3699477
PubMed Central ID:	PMC3699477
PubMed ID:	23844149
Date Deposited:	30 Aug 2013 16:59
Last Modified:	20 Dec 2018 00:55
URI:	http://d-scholarship.pitt.edu/id/eprint/19504

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