Phosphodiesterase (PDE) inhibitors represent an important advance in the treatment of @entity323 ( @entity323 ). In spite of widespread use and generally good efficacy, as a class they remain ineffective in 15-57% of @entity1 . Specific cohorts of @entity1 with severe vascular or neurogenic basis to their @entity323 , such as @entity6 @entity1 or those who have undergone radical pelvic surgery, demonstrate lower response rates with PDE inhibition treatment. We believe that circulating levels of @entity842 (NO) may be enhanced through delivery of adequate concentrations of free @entity26 radical scavenger molecules such as @entity270 . Higher levels of NO, theoretically, should produce increased penile blood flow with the potential for a synergistic effect when combined with a @entity7856 inhibitor. With this hypothesis in mind, 20 adult male Sprague-Dawley @entity3839 -induced (60 mg/kg i.p.) @entity6 @entity35 were divided into four therapeutic groups (n=5). Group I--control animals received peanut oil, group II-- @entity270 20 IU/day, group III-- @entity7855 5 mg/kg/day and group IV-- @entity270 20 IU/day plus @entity7855 5 mg/kg/day, by oral gavage daily for 3 weeks. Erectile function was assessed as a rise in intracavernous pressure following cavernous nerve electrostimulation. Penile tissue was harvested to determine the changes in tissue morphology including neuronal @entity842 synthase, smooth muscle alpha-actin and endothelial cell integrity. @entity7856 protein content and activity were measured. Significant increases in intracavernous pressure were measured in the animals receiving combined @entity270 plus @entity7855 treatment. Immunohistochemical staining showed increases of neuronal @entity842 synthase, endothelial cell and smooth muscle cell staining. Western blot analysis did not show significant differences of @entity7856 protein between the groups. However, higher @entity7856 activity was measured in the @entity7855 group and lower activity of @entity7856 was recorded in the cohort receiving @entity270 with @entity7855 . @entity270 enhanced the therapeutic effect of the @entity7856 inhibitor in a meaningful way in this animal model of @entity6 . This study indicates a potential means of salvaging erectile function among @entity1 who are refractory to @entity7855 .

Effect of @entity7856 inhibition combined with free @entity26 radical scavenger therapy on erectile function in a XXXX animal model.

@entity1 :: ('9606', 'Species') :: ['patients', 'men'] @entity323 :: ('MESH:D007172', 'Disease') :: ['erectile dysfunction', 'ED'] @entity7856 :: ('8654', 'Gene') :: ['PDE5'] @entity270 :: ('MESH:D014810', 'Chemical') :: ['Vitamin E', 'vitamin E'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetic', 'diabetes'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity3839 :: ('MESH:D013311', 'Chemical') :: ['streptozotocin'] @entity7855 :: ('MESH:C101426', 'Chemical') :: ['sildenafil'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity35 :: ('10116', 'Species') :: ['rats']
@entity6 :: (MESH:D003920,Disease) :: ['diabetic']
