FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms.

FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. Abstract Text:

Gwen Lagoda,Liming Jin,Todd J Lehrfeld,Tongyun Liu,Arthur L Burnett,

INTRODUCTION: Immunophilin ligands and phosphodiesterase type 5 (PDE5) inhibitors are touted to promote erectile function recovery after cavernous nerve (CN) injury. However, the mechanisms for their effects remain unclear. AIM: To compare the erection recovery effects of the immunophilin ligand FK506 and the PDE5 inhibitor sildenafil after CN injury and determine whether they involve antioxidative and/or antiapoptotic mechanisms. METHODS: Initial experiments established conditions of our CN injury model in adult male Sprague-Dawley rats. Subsequently, we evaluated treatment effects 14 days after: (i) unilateral CN injury (UNI) + saline (vehicle control); (ii) UNI + FK506 (5 mg/kg once daily, subcutaneous x 5 days); (iii) UNI + sildenafil (20 mg/kg every 8 hours, subcutaneous x 7 days); (iv) UNI + FK506/sildenafil; and (v) sham surgery. MAIN OUTCOME MEASURES: Intracavernous pressure (ICP) measurement after CN electrical stimulation to assess erectile function and Western blot analysis of expressions of glutathione peroxidase (GPX; antioxidant enzyme), nitrotyrosine (NT; oxidative stress marker), and phosphorylated and total Akt (antiapoptotic factor) in penes. RESULTS: In the UNI model, GPX expression was increased at Days 1 and 7, while p-Akt expression decreased at Day 1 and returned to baseline at Day 7. GPX expression was significantly higher in the UNI + FK506 group compared with the saline-treated group (P < 0.05). ICP increased in all treatment groups compared with that of the saline-treated group (P < 0.05). NT levels were increased after saline treatment (P < 0.05) but not after FK506 and sildenafil treatment, alone or in combination. GPX was localized to nerves coursing through the penis and to smooth muscle and endothelium of the dorsal vein and arteries. CONCLUSIONS: Both FK506 and sildenafil protect erectile function after CN injury by decreasing oxidative stress-associated tissue damage. FK506 may act through increased GPX activity. Further research is required to elucidate mechanisms associated with the beneficial effect of sildenafil.

FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. Publishing Authors By Initials

G Lagoda,L Jin,TJ Lehrfeld,T Liu,AL Burnett,

For similar chemical actions and uses: pharmacologic actions: therapeutic uses: cardiovascular agents: vasodilator agents research abstracts see: chemical actions and uses: pharmacologic actions: therapeutic uses: cardiovascular agents: vasodilator agents research

PUBMED ID PMID:

MEDLINE DATE:

FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The journal of sexual medicine

VOLUME: 4

Page Numbers: 908-16

Journal Abbreviation:

ISSN: 1743-6095

DAY: 3

MONTH: Jul

YEAR: 2007

FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101230693

FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. Keywords Mesh Terms:

KEYWORDS: Vasodilator Agents

MESH TERMS: pharmacology

Chemical & Substance for Abstract: FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. Information

Substance Name: Nitric Oxide Synthase

Registry Number: EC 1.14.13.39

Grant and Affiliation Information for FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms.

AFFILIATION: Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, 600 N. Wolfe Street/Marburg 407, Baltimore, MD 21287, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK 064679

ACRONYM: DK

MEDLINETA: J Sex Med

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms Related Publications

• A method for isolating living polymorphonuclear leukocytes from peripheral blood.
• An early regime for severe finger injuries.
• Anomalous channel between aorta and right ventricle; report of a case.
• Association between maternal exposure to ambient air pollutants during pregnancy and fetal growth restriction.
• BNP-induced activation of cGMP in human cardiac fibroblasts: interactions with fibronectin and natriuretic peptide receptors.
• Cystic emphysema of the lungs.
• Des-serine-proline brain natriuretic peptide 3-32 in cardiorenal regulation.
• Distinct roles for renal particulate and soluble guanylyl cyclases in preserving renal function in experimental acute heart failure.
• Does androgen suppression plus radiation therapy lead to changes in penile length in prostate cancer patients?
• Effectiveness of repellents applied to clothing for protection against salt-marsh mosquitoes.
• Erectile function outcomes in the current era of anatomic nerve-sparing radical prostatectomy.
• Erythropoietin receptor expression in the human urogenital tract: immunolocalization in the prostate, neurovascular bundle and penis.
• Ethical considerations in the use of DNA for the diagnosis of diseases.
• FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms.
• Large-scale purification and crystallization of adenovirus hexon.
• MRC trials in acute myeloblastic luekemia: Where have we got to?
• Meta-Analysis of Neuropsychological Symptoms of Adolescents and Adults with PKU.
• Molecular Pharmacotherapeutic Targeting of PDE5 for Preservation of Penile Health.
• NADPH oxidase: recent evidence for its role in erectile dysfunction.
• Oral brain natriuretic peptide: a novel strategy for chronic protein therapy for cardiovascular disease.
• Periodically poled BaMgF(4) for ultraviolet frequency generation.
• Refractivity of nitrogen gas in the vacuum ultraviolet.
• Review of meningioma histopathology.
• Rights and the reality of healthcare charging in the United Kingdom.
• Roaches; how to identify and principles of control.
• Sapropterin dihydrochloride (Kuvan/phenoptin), an orally active synthetic form of BH4 for the treatment of phenylketonuria.
• The perforated appendix.
• Unusual strangulated hernias in infants.
• Validation and feasibility of intraoperative three-dimensional transesophageal echocardiographic cardiac output.
• Vulnerable elders: when it is no longer safe to live alone.