Adenosine actions are preserved in corpus cavernosum from obese and type II diabetic db/db mouse

Fernando Silva Carneiro, Fernanda R.C. Giachini, Victor V. Lima, Zidonia N. Carneiro, Romulo Leite, Edward W. Inscho, Rita C. Tostes, R Clinton Webb

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Introduction. Erectile dysfunction (ED) in diabetes is associated with autonomic neuropathy and endothelial dysfunction. Whereas the nonadrenergic-noncholinergic (NANC)/neurogenic nitric oxide pathway has received great attention in diabetes-associated ED, few studies have addressed sympathetic overactivity. Aim. To test the hypothesis that adenosine-induced inhibition of adrenergic-mediated contractile responses in mouse corpus cavernosum is impaired in the presence of diabetes. Methods. The db/db (obesity and type II diabetes caused by a leptin receptor mutation) mouse strain was used as a model of obesity and type II diabetes, and standard procedures were performed to evaluate functional cavernosal responses. Main Outcome Measures. Increased cavernosal responses to sympathetic stimulation in db/db mice are not associated with impaired prejunctional actions of adenosine. Results. Electrical field stimulation (EFS)-, but not phenylephrine (PE)-, induced contractions are enhanced in cavernosal strips from db/db mice in comparison with those from lean littermates. Direct effects of adenosine, 2-chloro-adenosine, A 1 receptor agonist C-8031 (N6 cyclopentyladenosine), and sodium nitroprusside are similar between the strips from lean and db/db mice, whereas relaxant responses to acetylcholine and NANC stimulation are significantly impaired in the cavernosal strips from db/db mice. 5′-Iodotubercidin (adenosine kinase inhibitor) and dipyridamole (inhibitor of adenosine transport), as well as the A 1 agonist C-8031, significantly and similarly inhibit contractions induced by stimulation of adrenergic nerves in the cavernosal strips from lean and db/db mice. Conclusions. Results from this study suggest that corpora cavernosa from obese and diabetic db/db mice display altered neural-mediated responses that would favor penile detumescence, i.e., increased contractile response to adrenergic nerve stimulation and decreased relaxant responses upon activation of NANC nerves. However, increased cavernosal responses to adrenergic nerve stimulation are not due to impaired negative modulation of sympathetic neurotransmission by adenosine in this diabetic model.

Original languageEnglish (US)
Pages (from-to)1156-1166
Number of pages11
JournalJournal of Sexual Medicine
Volume5
Issue number5
DOIs
StatePublished - May 1 2008

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Adenosine
Adrenergic Agents
Erectile Dysfunction
Type 2 Diabetes Mellitus
Obesity
2-Chloroadenosine
Adenosine Kinase
Dipyridamole
Nitroprusside
Phenylephrine
Synaptic Transmission
Electric Stimulation
Acetylcholine
Nitric Oxide
Outcome Assessment (Health Care)
Mutation

Keywords

  • Adenosine
  • AnimalModels
  • Diabetes
  • Obesity
  • Sympathetic Neurotransmission

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Urology

Cite this

Adenosine actions are preserved in corpus cavernosum from obese and type II diabetic db/db mouse. / Carneiro, Fernando Silva; Giachini, Fernanda R.C.; Lima, Victor V.; Carneiro, Zidonia N.; Leite, Romulo; Inscho, Edward W.; Tostes, Rita C.; Webb, R Clinton.

In: Journal of Sexual Medicine, Vol. 5, No. 5, 01.05.2008, p. 1156-1166.

Research output: Contribution to journalArticle

Carneiro, FS, Giachini, FRC, Lima, VV, Carneiro, ZN, Leite, R, Inscho, EW, Tostes, RC & Webb, RC 2008, 'Adenosine actions are preserved in corpus cavernosum from obese and type II diabetic db/db mouse', Journal of Sexual Medicine, vol. 5, no. 5, pp. 1156-1166. https://doi.org/10.1111/j.1743-6109.2007.00752.x
Carneiro, Fernando Silva ; Giachini, Fernanda R.C. ; Lima, Victor V. ; Carneiro, Zidonia N. ; Leite, Romulo ; Inscho, Edward W. ; Tostes, Rita C. ; Webb, R Clinton. / Adenosine actions are preserved in corpus cavernosum from obese and type II diabetic db/db mouse. In: Journal of Sexual Medicine. 2008 ; Vol. 5, No. 5. pp. 1156-1166.
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AU - Carneiro, Zidonia N.

AU - Leite, Romulo

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AU - Webb, R Clinton

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N2 - Introduction. Erectile dysfunction (ED) in diabetes is associated with autonomic neuropathy and endothelial dysfunction. Whereas the nonadrenergic-noncholinergic (NANC)/neurogenic nitric oxide pathway has received great attention in diabetes-associated ED, few studies have addressed sympathetic overactivity. Aim. To test the hypothesis that adenosine-induced inhibition of adrenergic-mediated contractile responses in mouse corpus cavernosum is impaired in the presence of diabetes. Methods. The db/db (obesity and type II diabetes caused by a leptin receptor mutation) mouse strain was used as a model of obesity and type II diabetes, and standard procedures were performed to evaluate functional cavernosal responses. Main Outcome Measures. Increased cavernosal responses to sympathetic stimulation in db/db mice are not associated with impaired prejunctional actions of adenosine. Results. Electrical field stimulation (EFS)-, but not phenylephrine (PE)-, induced contractions are enhanced in cavernosal strips from db/db mice in comparison with those from lean littermates. Direct effects of adenosine, 2-chloro-adenosine, A 1 receptor agonist C-8031 (N6 cyclopentyladenosine), and sodium nitroprusside are similar between the strips from lean and db/db mice, whereas relaxant responses to acetylcholine and NANC stimulation are significantly impaired in the cavernosal strips from db/db mice. 5′-Iodotubercidin (adenosine kinase inhibitor) and dipyridamole (inhibitor of adenosine transport), as well as the A 1 agonist C-8031, significantly and similarly inhibit contractions induced by stimulation of adrenergic nerves in the cavernosal strips from lean and db/db mice. Conclusions. Results from this study suggest that corpora cavernosa from obese and diabetic db/db mice display altered neural-mediated responses that would favor penile detumescence, i.e., increased contractile response to adrenergic nerve stimulation and decreased relaxant responses upon activation of NANC nerves. However, increased cavernosal responses to adrenergic nerve stimulation are not due to impaired negative modulation of sympathetic neurotransmission by adenosine in this diabetic model.

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