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 language | English (US) |
|---|---|
| Pages (from-to) | 1156-1166 |
| Number of pages | 11 |
| Journal | Journal of Sexual Medicine |
| Volume | 5 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2008 |
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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 journal › Article
}
TY - JOUR
T1 - Adenosine actions are preserved in corpus cavernosum from obese and type II diabetic db/db mouse
AU - Carneiro, Fernando Silva
AU - Giachini, Fernanda R.C.
AU - Lima, Victor V.
AU - Carneiro, Zidonia N.
AU - Leite, Romulo
AU - Inscho, Edward W.
AU - Tostes, Rita C.
AU - Webb, R Clinton
PY - 2008/5/1
Y1 - 2008/5/1
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.
AB - 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.
KW - Adenosine
KW - AnimalModels
KW - Diabetes
KW - Obesity
KW - Sympathetic Neurotransmission
UR - http://www.scopus.com/inward/record.url?scp=42949138452&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42949138452&partnerID=8YFLogxK
U2 - 10.1111/j.1743-6109.2007.00752.x
DO - 10.1111/j.1743-6109.2007.00752.x
M3 - Article
C2 - 18221284
AN - SCOPUS:42949138452
VL - 5
SP - 1156
EP - 1166
JO - Journal of Sexual Medicine
JF - Journal of Sexual Medicine
SN - 1743-6095
IS - 5
ER -