OBJECTIVES: The Ras homolog gene family, member A (RhoA) and its main downstream effector, Rho-kinase (ROCK) are important in maintaining the penis in the flaccid state. The pathophysiology of sickle cell disease-associated priapism is not well defined. We hypothesized that the RhoA/ROCK vasoconstrictive pathways might be involved in the development of priapism. Therefore, the objective of the present study was to evaluate the molecular changes in RhoA and ROCK in an established transgenic sickle cell mouse model of priapism. METHODS: Two groups of mice were used: wild type (WT; C57BL/6) mice and transgenic sickle cell mice. We evaluated RhoA guanosine triphosphatase and total ROCK activities, as well as ROCK1 and ROCK2 protein expression, in WT and sickle mice penises. We also evaluated the in vivo erectile responses to cavernous nerve stimulation and the frequency and duration of spontaneous erections before and after cavernous nerve stimulation. RESULTS: Sickle mice demonstrated significantly (P <.05) enhanced erectile responses to cavernous nerve stimulation and frequency of spontaneous erections both before and after cavernous nerve stimulation compared with the WT mice. The sickle mice penises had a significant decline in RhoA guanosine triphosphatase (P <.01) and total ROCK activities (P <.05) compared with the WT mice. A significant (P <.05) reduction in ROCK2 protein expression in sickle mice penises compared with WT mice protein expression. No change in ROCK1 protein expression was observed in either cohort of mice penises. CONCLUSIONS: These data suggest that sickle cell disease associated-priapism might be contributed by a lack of RhoA/ROCK-mediated vasoconstriction and highlight a novel molecular mechanism in the pathophysiology of priapism. Copyright 2010 Elsevier Inc. All rights reserved.
OBJECTIVES: The Ras homolog gene family, member A (RhoA) and its main downstream effector, Rho-kinase (ROCK) are important in maintaining the penis in the flaccid state. The pathophysiology of sickle cell disease-associated priapism is not well defined. We hypothesized that the RhoA/ROCK vasoconstrictive pathways might be involved in the development of priapism. Therefore, the objective of the present study was to evaluate the molecular changes in RhoA and ROCK in an established transgenic sickle cell mouse model of priapism. METHODS: Two groups of mice were used: wild type (WT; C57BL/6) mice and transgenic sickle cell mice. We evaluated RhoA guanosine triphosphatase and total ROCK activities, as well as ROCK1 and ROCK2 protein expression, in WT and sickle mice penises. We also evaluated the in vivo erectile responses to cavernous nerve stimulation and the frequency and duration of spontaneous erections before and after cavernous nerve stimulation. RESULTS: Sickle mice demonstrated significantly (P <.05) enhanced erectile responses to cavernous nerve stimulation and frequency of spontaneous erections both before and after cavernous nerve stimulation compared with the WT mice. The sickle mice penises had a significant decline in RhoA guanosine triphosphatase (P <.01) and total ROCK activities (P <.05) compared with the WT mice. A significant (P <.05) reduction in ROCK2 protein expression in sickle mice penises compared with WT mice protein expression. No change in ROCK1 protein expression was observed in either cohort of mice penises. CONCLUSIONS: These data suggest that sickle cell disease associated-priapism might be contributed by a lack of RhoA/ROCK-mediated vasoconstriction and highlight a novel molecular mechanism in the pathophysiology of priapism. Copyright 2010 Elsevier Inc. All rights reserved.
Authors: Lewis L Hsu; Hunter C Champion; Sally A Campbell-Lee; Trinity J Bivalacqua; Elizabeth A Manci; Bhalchandra A Diwan; Daniel M Schimel; Audrey E Cochard; Xunde Wang; Alan N Schechter; Constance T Noguchi; Mark T Gladwin Journal: Blood Date: 2007-04-01 Impact factor: 22.113
Authors: Tiejuan Mi; Shahrzad Abbasi; Hong Zhang; Karen Uray; Janci L Chunn; Ling Wei Xia; Jose G Molina; Norman W Weisbrodt; Rodney E Kellems; Michael R Blackburn; Yang Xia Journal: J Clin Invest Date: 2008-04 Impact factor: 14.808
Authors: Mário Angelo Claudino; Carla Fernanda Franco-Penteado; Marcus Alexandre Finzi Corat; Ana Paula Gimenes; Luiz Augusto Correa Passos; Edson Antunes; Fernando Ferreira Costa Journal: J Sex Med Date: 2009-06-02 Impact factor: 3.802
Authors: Trinity J Bivalacqua; Biljana Musicki; Lewis L Hsu; Mark T Gladwin; Arthur L Burnett; Hunter C Champion Journal: J Sex Med Date: 2009-06-11 Impact factor: 3.802