Molecular evaluation of the ameliorative effect of chronic sildenafil administration on erectile function in a rat model of chronic renal failure

Erectile dysfunction (ED), is one of the important health problems that affects life quality of couples and its treatment success fairly reduces in systemic diseases. The relation between AGE (Advanced Glycation End Product) molecules and ED which is developed related to DM (Diabetes Mellitus) and CRF (Chronic Renal Failure) are demonstrated in various studies. In this study, the ameliorative effects of administration of chronic sildenafil treatment on molecules play role in erectile physiology and erectile functions are aimed to be evaluated in a rat model of CRF. 3 groups of Wistar male rats were used in the present study. 8 rats were used in the Control group. In the second (n=9) and third groups (n=8), single side total and counter side 5/6 nephrectomy operations were applied to develop a CRF model as stated in the literature. After that, rats in the third group were taken 5 mg/kg sildenafil treatment p.o daily. BUN (Blood Urea Nitrogen) and creatinine levels were measured from the tail blood samples of rats. At the end of the study, cavernosal nerve stimulation (CNS) were applied in all rats to evaluate the erectile capacity. ICP/MAP and total ICP (Area Under Curve; AUC) levels were analyzed. MDA, 5-HMF, cGMP, nNOS and iNOS protein expressions were evaluated in rat cavernosal tissues. In CRF developed rats, serum BUN and creatinine levels were found to be significantly higher compared to the control group (p<0,05). Erectile responses were observed to be lesser in CRF developed rats. Levels of ICP/MAP and total ICP were significantly lower in the second group of rats compared to the control group (p<0,05). Chronic treatment of sildenafil cured erectile responses. ICP/MAP and total ICP levels were found to be higher in rats that were given treatment. The improvement in the levels of ICP/MAP and total ICP was observed to approach to the control group in 5 v and 7.5 v measurements and it was statistically significant compared to the CRF group (p<0,05). The level of 5-HMF, the product of MDA and AGE, is an indication of tissue damage and was observed to be significantly higher in CRF developed rats. With chronic sildenafil treatment, both MDA and 5-HMF levels were found to be significantly lower compared to the CRF group (p<0.05). cGMP level and nNOS protein expression play roles in erectile physiology and were found to be significantly decreased in CRF developed rats compared to the control group (p<0,05); chronic sildenafil treatment increased the levels of both molecules and approached their levels to the control group. This improvement was also statistically significant (p<0,05). Also in a similar way, iNOS protein expression which was increased due to CRF, was decreased with the treatment of cronic sildenafil. Compared to the CRF group, this attenuation in the treatment given rats was observed to be statistically significant (p<0,05). In our study, it was demonstrated that erectile response was reduced significantly and AGE levels were increased in cavernosal tissue in rats in which CRF model was developed similar to the literature. Chronic sildenafil treatment decreased AGE levels, increased levels of molecules that play key roles in erectile physiology and thus cured erectile responses. The results of our study show the protective effects of chronic sildenafil treatment on endotelial functions and shed light on the fact that new approaches will become possible in agenda in terms of ED treatment in this patient group.