Document Detail


Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats.
MedLine Citation:
PMID:  14963467     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Erectile dysfunction associated with diabetes mellitus is caused in part by disordered endothelial smooth muscle relaxation, neuropathy, and a decrease in cavernosal nitric oxide synthase (NOS) activity. The purpose of this study was to determine whether a combination of sildenafil and adenoviral gene transfer of endothelial NOS (eNOS) could enhance the erectile response in diabetic rats. Five groups of animals were utilized: (1) age-matched control rats, (2) streptozotocin (STZ)-induced diabetic rats (60 mg/kg i.p.), (3) STZ-rats + sildenafil (2 mg/kg i.v.), (4) STZ-rats transfected with AdCMVbetagal or AdCMVeNOS, and (5) STZ-rats transfected with AdCMVeNOS +sildenafil (2 mg/kg i.v.). At 2 months after i.p. injection of STZ, groups 4 and 5 were transfected with the adenoviruses and 1-2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Cyclic 3',5'-guanosine monophosphate (cGMP) levels were assessed in the cavernosal tissue. STZ-diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve; AUC) after CNS when compared to control rats. STZ-diabetic rats+AdCMVeNOS had a peak ICP and AUC, which were similar to control animals. STZ-diabetic rats administered sildenafil demonstrated a significant increase in peak ICP at the 5 and 7.5 V settings, while the AUC was significantly increased at all voltage (V) settings. The increase in both ICP and AUC of STZ-diabetic rats transfected with AdCMVeNOS at all V settings was greater than STZ-diabetic rats transfected with AdCMVbetagal. STZ-diabetic rats transfected with AdCMVeNOS and administered sildenafil had a significant increase in total ICP that was greater than eNOS gene therapy alone. Cavernosal cGMP levels were significantly decreased in STZ-diabetic rats, but were increased after transfection with AdCMVeNOS to values greater than control animals. In conclusion, overexpression of eNOS and cGMP in combination with sildenafil significantly increased both the peak ICP and total ICP to CNS in the STZ-diabetic rat, which was similar to the response observed in control rats. Moreover, the total erectile response was greater in STZ-diabetic rats receiving eNOS gene therapy plus sildenafil than STZ-rats receiving sildenafil or eNOS gene therapy alone.
Authors:
T J Bivalacqua; M F Usta; H C Champion; S Leungwattanakij; P A Dabisch; D B McNamara; P J Kadowitz; W J G Hellstrom
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of impotence research     Volume:  16     ISSN:  0955-9930     ISO Abbreviation:  Int. J. Impot. Res.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-02-13     Completed Date:  2004-08-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9007383     Medline TA:  Int J Impot Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  21-9     Citation Subset:  IM    
Affiliation:
Department of Urology, Tulane University School of Medicine, New Orleans, Louisana 70112, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Combined Modality Therapy
Cyclic GMP / metabolism
Diabetes Mellitus, Experimental / complications
Erectile Dysfunction / drug therapy*,  etiology
Gene Therapy*
Male
Nitric Oxide Synthase / genetics*
Nitric Oxide Synthase Type III
Penile Erection / drug effects
Piperazines / pharmacology*
Purines
Rats
Rats, Inbred Strains
Sulfones
Transfection
Vasodilator Agents / pharmacology*
Chemical
Reg. No./Substance:
0/Piperazines; 0/Purines; 0/Sulfones; 0/Vasodilator Agents; 139755-83-2/sildenafil; 7665-99-8/Cyclic GMP; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, rat

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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