Reduction of Endothelial and Smooth Muscle Density in the Corpora Cavernosa of the Streptozotocin Induced Diabetic Rat

Burchardt, Tatjana; Burchardt, Martin; Karden, J.; Buttyan, Ralph; Shabsigh, Ahmad; Taille, Alexandre de la; Ng, Pui Yee; ANASTASIADIS, A. G.; Shabsigh, Ridwan

doi:10.1016/s0022-5347(05)67111-x

Cited by 77 publications

(57 citation statements)

References 37 publications

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“…Twentyone days post CN resection the endothelial layer was almost completely absent. This result was very similar to endothelial disruption observed in the streptozotocin-model of diabetes 42 which exhibits neuropathy and ED. Further analysis is required to determine if NOS therapy could remodel the corpora to resemble the normal architecture.…”

Section: Discussionsupporting

confidence: 85%

Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction

et al. 2001

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Optimal treatment of erectile dysfunction (ED) following radical prostatectomy remains a subject of much controversy and is a significant concern for prostate cancer patients requiring surgical intervention. Neural stimulation involving nitric oxide synthase (NOS) is a crucial aspect of the normal erection process. In this study NOS isoform interaction was evaluated to improve our understanding of molecular changes pertaining to erection post radical prostatectomy. Bilateral cavernous nerve (CN) resected and control adult male Sprague-Dawley rats were killed 7, 14 and 21 days after injury. RT-PCR, in situ hybridization, Western blot and immunohistochemical analysis were used to evaluate changes in NOS isoform expression and distribution. NOS-I protein was dramatically decreased after CN injury while NOS-III and NOS-II remained unchanged. A profound decrease in smooth muscle and endothelium was observed in the corpora. To our knowledge this is the first report of differential altered NOS isoform protein abundance under conditions which mimic radical prostatectomy. These results show the importance of maintaining at least partial innervation of the penis after surgical intervention and that endothelial and smooth muscle changes resulting from loss of innervation may account for the ED observed in prostatectomy patients.

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Section: Discussionsupporting

confidence: 85%

Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction

et al. 2001

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“…The meaning is uncertain, especially when it is compared with the SMC density at the tail artery, a muscular vessel widely used in the study of vascular SM (Leal et al 2008), whose age-related features under controlled and dietary experimental conditions are here described for the first time. Loss of SMC and increment of CT deposition along aging have been repeatedly reported in corporal tissue either in animal models (Burchard et al 2000;Carrier et al 1997) and humans (Tomada et al 2011). These changes provoke mechanical alterations of the penis, as reduction in its elasticity and compliance, which lead to erectile function impairment (Ferrini et al 2009).…”

Section: Discussionmentioning

confidence: 96%

Energy restriction ameliorates metabolic syndrome-induced cavernous tissue structural modifications in aged rats

Tomada

Fernandes

Guimarães

et al. 2012

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High-fat (HF) diet regular intake along life highly contributes to vascular dysfunction and to an increment in prevalence of metabolic syndrome (MetS) and erectile dysfunction (ED), a surrogate symptom of occult vascular disease, in the elderly. However, little is known about the effects of energy restriction (ER) alone/or after an HF-feeding period. We show here that in male Sprague-Dawley rats, 16 months of HF-diet consumption led to an increase in body adiposity, blood pressure, lipidemia, C-reactive protein, and insulin resistance and to hypoadiponectinemia, conditions that cluster in MetS. In addition, this treatment strongly favored collagen deposition in cavernous tissue and myocardium. Conversely, for the same time period, the ingestion of 75 % of ad libitum energy intake by controls (ER) extensively counteracted these outcomes. The impact of 6-month ER after 10-month HF period was also analyzed, and despite the decrease in body weight, adiposity, blood pressure, lipidemia, and Creactive protein and improvement of insulin sensitivity, no differences were observed either in adiponectin blood levels or in retroperitoneal fat pad mass. Moreover, this treatment led to a reduction in cavernous tissue collagen deposition, but not in the myocardium, and evidenced differential mobilization of adipose tissue accretions. The data show the ability of HF diet to cause MetS and produce unwanted effects on myocardium and corpora vascular structure. They also indicate that these consequences are preventable upon ER diet starting early, but not later, in life.

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“…[45][46][47] The addition of daily vitamin E supplements to sildenafil appeared to act in a synergistic fashion, increasing the response to electric-stimulated penile pressure and an improved nNOS, endothelial cells and smooth muscle content. Although the triglyceride levels did not achieve statistical significance, the observed differences among our groups may have in part contributed to the measured changes.…”

Section: Vitamin E Vit E + Sildenafilmentioning

confidence: 98%

Effect of PDE5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model

Young

Freeman

et al. 2003

Int J Impot Res

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Phosphodiesterase (PDE) inhibitors represent an important advance in the treatment of erectile dysfunction (ED). In spite of widespread use and generally good efficacy, as a class they remain ineffective in 15-57% of men. Specific cohorts of patients with severe vascular or neurogenic basis to their ED, such as diabetic men or those who have undergone radical pelvic surgery, demonstrate lower response rates with PDE inhibition treatment. We believe that circulating levels of nitric oxide (NO) may be enhanced through delivery of adequate concentrations of free oxygen radical scavenger molecules such as vitamin E. Higher levels of NO, theoretically, should produce increased penile blood flow with the potential for a synergistic effect when combined with a PDE5 inhibitor. With this hypothesis in mind, 20 adult male Sprague-Dawley streptozotocin-induced (60 mg/kg i.p.) diabetic rats were divided into four therapeutic groups (n ¼ 5). Group IFcontrol animals received peanut oil, group IIFvitamin E 20 IU/day, group IIIFsildenafil 5 mg/kg/day and group IVFvitamin E 20 IU/day plus sildenafil 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 nitric oxide synthase, smooth muscle a-actin and endothelial cell integrity. PDE5 protein content and activity were measured. Significant increases in intracavernous pressure were measured in the animals receiving combined vitamin E plus sildenafil treatment. Immunohistochemical staining showed increases of neuronal nitric oxide synthase, endothelial cell and smooth muscle cell staining. Western blot analysis did not show significant differences of PDE5 protein between the groups. However, higher PDE5 activity was measured in the sildenafil group and lower activity of PDE5 was recorded in the cohort receiving vitamin E with sildenafil. Vitamin E enhanced the therapeutic effect of the PDE5 inhibitor in a meaningful way in this animal model of diabetes. This study indicates a potential means of salvaging erectile function among patients who are refractory to sildenafil.

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Reduction of Endothelial and Smooth Muscle Density in the Corpora Cavernosa of the Streptozotocin Induced Diabetic Rat

Cited by 77 publications

References 37 publications

Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction

Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction

Energy restriction ameliorates metabolic syndrome-induced cavernous tissue structural modifications in aged rats

Effect of PDE5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model

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