Abnormal protein expression in the corpus cavernosum impairs erectile function in type 2 diabetes.
OBJECTIVE
To investigate the changes in corporal relaxation, intracavernous pressure (ICP) and associated protein expression that control normal erectile function in rats with type 2 diabetes (T2D), as this disease is part of the 'metabolic syndrome' associated with a high rate of erectile dysfunction (ED) in men, resulting from failure of corpus cavernosum-mediated processes.


METHODS
T2D was induced in rats by feeding them with a high-fat diet (HFD) followed by an injection with low-dose streptozotocin (STZ); they were then compared with rats that received a normal diet (ND).


RESULTS
Hyperglycaemia and dyslipidaemia were induced in HFD + STZ rats, suggesting that T2D was established. The rats with T2D had associated ED, as both nonadrenergic noncholinergic-mediated corporal relaxation and increased ICP by cavernous nerve stimulation were significantly attenuated compared to the ND group. Western blot analysis revealed diabetes-associated lower expression of endothelial and neuronal nitric oxide synthase (e and nNOS), and cGMP-dependent protein kinase (PKG)-1alpha/beta expression in penile tissue than in the ND group. Contrary to the proteins that regulate corporal relaxation, there were relatively high levels of RhoA/Rho kinase receptor 1 (ROCK1) and ET-A receptor (ETAR) in T2D rats. However, the expressed level of phosphodiesterase-5 and insulin-like growth factor binding protein 3 was not altered significantly in response to T2D.


CONCLUSIONS
Decreased expression of certain proteins that mediate the relaxant mechanism, associated with increased expression of certain proteins that mediate contractile mechanisms, might be important in the development of T2D-associated ED. In particular, down-regulated eNOS/nNOS/PKG1 as well as up-regulated ETAR/RhoA/ROCK1 might participate in the aetiology of ED in T2D.
Chiou
Wen-Fei
WF
National Research Institute of Chinese Medicine, Taipei, Taiwan. wfchiou@cma23.nricm.edu.tw
Liu
Hui-Kang
HK
Juan
Chi-Wen
CW
D000818:Animals; D015153:Blotting, Western; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D007172:Erectile Dysfunction / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000378:metabolism* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases / Q000378:metabolism
D019001:Nitric Oxide Synthase; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D017869:Cyclic GMP-Dependent Protein Kinases