Effect of DDAH/ADMA/NOS regulation pathway on cavernae corporum cavernosorum rat penis of different age

Abstract

The effect of DDAH/ADMA/NOS pathway in penile tissue of rats of different age was investigated to better understand the mechanism of age-related erectile dysfunction (ED). The Sprague Dawley male rats were assigned as the young group (3month old, n=10) and the old group (18month old, n=10) respectively. Intracavernous pressure (ICP) was measured before and after papaverine intracavernous injection. Pathology structure of penile tissue was evaluated under transmission electron microscope. The expression amounts of asymmetric dimethylarginine (ADMA) and cyclic guanosine monophosphate (cGMP) in penile tissue were detected by ELISA; the expression levels of isoform-specific DDAH and NOS were assessed via Western blot. Compared with the young group, the ICP in the old group rat decreased significantly (33.46±5.37 versus 39.71±3.67mmHg, P=0.02) after papaverine injection. Diffused fibrosis and impairment of endothelial cell were observed in corpus cavernosum in the old group rats. Higher level of ADMA (10.83±0.96 versus 7.51±1.39μmol per gpro, P=3.14×10-4) and lower level of cGMP (29.42±3.84 versus 47.09±6.07nmol per gpro, P=1.57×10-6) were detected in penile tissue of the old group compared with those of the young group. Expression of DDAH1, DDAH2, endothelial NOS (eNOS) and neuronal NOS(nNOS) all decreased significantly in penile tissue of the old group rat. The DDAH/ADMA/NOS regulation pathway changes dramatically accompanying with lower ICP in old group rat compared with those of the young group. Such findings in rats are suggestive in understanding the mechanism of age-related ED in humans.