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Neuronal nitric oxide signaling regulates erection recovery after cavernous nerve injury.

ABSTRACT: Nitric oxide is the major neuronal mediator of penile erection but its role in erectile function status after cavernous nerve injury is uncertain. We determined the function of neuronal nitric oxide signaling in the pathobiology of erectile function recovery after partial cavernous nerve injury using genetic and pharmacological mouse experimental paradigms.Erectile function was evaluated in 5 to 7 wild-type and neuronal nitric oxide synthase-? knockout mice per group 1, 3 and 7 days after unilateral crush or sham injury, at day 7 in wild-type mice treated with the nitric oxide synthase inhibitor L-NAME (l-nitro arginine methyl ester) (Sigma-Aldrich®) at baseline and for 6 days after unilateral crush injury. Apoptosis in the penis was evaluated by Western blot analysis of p-Akt-S473, 3-nitrotyrosine and caspase-3 after bilateral crush injury.Intracavernous pressure was significantly decreased at 1, 3 and 7 days in wild-type mice but only at day 1 in knockout mice after unilateral crush injury compared with sham treatment values (p <0.05). L-NAME treated wild-type mice had improved erectile function compared with the vehicle treated group at day 7 after unilateral crush injury (p <0.05). In penes p-Akt-S473 was significantly decreased in vehicle treated (p <0.05) but not in L-NAME treated wild-type mice. In penes 3-nitrotyrosine was significantly decreased in L-NAME treated wild-type and vehicle treated knockout mice (p <0.05). Caspase-3 in penes was significantly increased in vehicle treated (p <0.05) but not in L-NAME treated wild-type mice and vehicle treated knockout mice.Neuronal nitric oxide signaling regulates erectile function recovery early after partial cavernous nerve injury, exerting an inhibitory role via the induction of apoptotic change in penile tissue. Therapeutic strategies to improve erectile function recovery after radical prostatectomy may consider targeting pathogenic sites of nitric oxide neurobiology.

SUBMITTER: Sezen SF

PROVIDER: S-EPMC4474518 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Neuronal nitric oxide signaling regulates erection recovery after cavernous nerve injury.

Sezen Sena F SF Lagoda Gwen G Burnett Arthur L AL

The Journal of urology 20111216 2

<h4>Purpose</h4>Nitric oxide is the major neuronal mediator of penile erection but its role in erectile function status after cavernous nerve injury is uncertain. We determined the function of neuronal nitric oxide signaling in the pathobiology of erectile function recovery after partial cavernous nerve injury using genetic and pharmacological mouse experimental paradigms.<h4>Materials and methods</h4>Erectile function was evaluated in 5 to 7 wild-type and neuronal nitric oxide synthase-α knocko ...[more]

PMID: 22177198

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Project description:ObjectiveClinical treatment of erectile dysfunction (ED) caused by cavernous nerve (CN) injury during pelvic surgery is difficult. Low-intensity pulsed ultrasound (LIPUS) can be a potential strategy for neurogenic ED (NED). However, whether Schwann cells (SCs) can respond to LIPUS stimulation signals is unclear. This study aims to elucidate the signal transmission between SCs paracrine exosome (Exo) and neurons stimulated by LIPUS, as well as to analyze the role and potential mechanisms of exosomes in CN repair after injury.MethodsThe major pelvic ganglion (MPG) neurons and MPG/CN explants were stimulated with LIPUS of different energy intensities to explore the appropriate LIPUS energy intensity. The exosomes were isolated and purified from LIPUS-stimulated SCs (LIPUS-SCs-Exo) and non-stimulated SCs (SCs-Exo). The effects of LIPUS-SCs-Exo on neurite outgrowth, erectile function, and cavernous penis histology were identified in bilateral cavernous nerve crush injury (BCNI)-induced ED rats.ResultsLIPUS-SCs-Exo group can enhance the axon elongation of MPG/CN and MPG neurons compared to SCs-Exo group in vitro. Then, the LIPUS-SCs-Exo group showed a stronger ability to promote the injured CN regeneration and SCs proliferation compared to the SCs-Exo group in vivo. Furthermore, the LIPUS-SCs-Exo group increased the Max intracavernous pressure (ICP)/mean arterial pressure (MAP), lumen to parenchyma and smooth muscle to collagen ratios compared to the SCs-Exo group in vivo. Additionally, high-throughput sequencing combined with bioinformatics analysis revealed the differential expression of 1689 miRNAs between the SCs-Exo group and the LIPUS-SCs-Exo group. After LIPUS-SCs-Exo treatment, the phosphorylated levels of Phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and forkhead box O (FoxO) in MPG neurons increased significantly compared to negative control (NC) and SCs-Exo groups.ConclusionOur study revealed that LIPUS stimulation could regulate the gene of MPG neurons by changing miRNAs derived from SCs-Exo, then activating the PI3K-Akt-FoxO signal pathway to enhance nerve regeneration and restore erectile function. This study had important theoretical and practical significance for improving the NED treatment.

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Neuronal nitric oxide signaling regulates erection recovery after cavernous nerve injury.

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Neuronal nitric oxide signaling regulates erection recovery after cavernous nerve injury.

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