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


OBJECTIVE
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.


METHODS
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.
Carneiro
Fernando Silva
FS
Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil;; Department of Physiology, Medical College of Georgia, Augusta, GA, USA. Electronic address: fcarneiro@mcg.edu.
Giachini
Fernanda R C
FRC
Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil;; Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
Lima
Victor V
VV
Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
Carneiro
Zidonia N
ZN
Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
Leite
Romulo
R
Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
Inscho
Edward W
EW
Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
Tostes
Rita C
RC
Department of Physiology, Medical College of Georgia, Augusta, GA, USA; Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
Webb
R Clinton
RC
Department of Physiology, Medical College of Georgia, Augusta, GA, USA.
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D004176:Dipyridamole / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D010413:Penis / Q000294:innervation* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; C034214:5-iodotubercidin; C058394:2-chloro-N(6)cyclopentyladenosine; D004176:Dipyridamole; D000248:Adenosine Kinase; D000241:Adenosine; D014372:Tubercidin; D000109:Acetylcholine