Chronic treatment with taurine ameliorates diabetes-induced dysfunction of nitric oxide-mediated neurogenic and endothelium-dependent corpus cavernosum relaxation in rats.

This study was aimed to examine the effect of chronic taurine treatment on corpus cavernosum dysfunction in diabetic rats and to investigate possible underlying mechanisms. Thirty male rats were randomized to three groups of 10 each, including control, diabetic, and taurine-treated diabetic. Diabetes was induced in rats by streptozotocin (STZ, single intraperitoneal dose of 50 mg/kg body weight). Taurine was administered orally for 12 weeks (1% w/v in drinking water) from the day on which STZ was injected. At the end of the 12th week, strips of corpus cavernosum were suspended in an organ bath system for functional studies. Nitric oxide (NO)-mediated endothelium-dependent and neurogenic corpus cavernosum relaxation were evaluated by acetylcholine (ACh, 0.1-100 μm) and electrical field stimulation (EFS, 30 V, 5 ms, 2-32 Hz), respectively. The expressions of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (Ser-1177), neuronal nitric oxide synthase (nNOS), NADPH oxidase subunit gp91(phox) , Rho A, and Rho kinase in corpus cavernosum were semi-quantitatively assessed by immunohistochemistry. Induction of diabetes resulted in significant inhibition of NO-mediated endothelium-dependent and neurogenic corpus cavernosum relaxation. Furthermore, eNOS, p-eNOS, and nNOS expressions decreased significantly in diabetic rats compared to controls, while gp91(phox) , RhoA and Rho kinase expressions increased significantly. The diminished relaxation response to ACh and EFS as well as diabetes-related changes in expressions of these proteins in corpus cavernosum of diabetic rats was significantly improved by taurine. Taurine treatment improves NO-mediated relaxations of corpus cavernosum in diabetic rats probably by inhibiting NADPH oxidase/Rho kinase pathways.

Dalaklioglu S ，Kuscu N ，Celik-Ozenci C ，Bayram Z ，Nacitarhan C ，Ozdem SS ... -  《-》

Pravastatin improves the impaired nitric oxide-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in aged rats.

Dalaklioglu S ，Sahin P ，Tasatargil A ，Celik-Ozenci C ... -  《-》

TNF-α, erectile dysfunction, and NADPH oxidase-mediated ROS generation in corpus cavernosum in high-fat diet/streptozotocin-induced diabetic rats.

Patients with diabetes-associated erectile dysfunction (ED) are characterized by an increase in circulating tumor necrosis factor-alpha (TNF-α). However, no study has indicated whether and how TNF-α plays a role in the pathogenesis of ED associated with diabetes. We examined the effects and potential mechanism of infliximab (INF), a chimeric monoclonal antibody to TNF-α, on reactive oxygen species (ROS) generation in corpus cavernosum and ED in diabetic rats. Four groups of male rats were used: age-matched normal controls; diabetic rats induced by a high-fat diet (HFD) combined with a single streptozotocin (STZ) injection (35 mg/kg body weight, intraperitoneal [i.p.]); nondiabetic rats receiving INF (5 mg/kg body weight/week, i.p.), and diabetic rats receiving INF. Erectile function was assessed with electrical stimulation of the cavernous nerve after 8 weeks. The blood and penile tissues were harvested for plasma biochemical determinations, serum TNF-α measurement, penile ROS detection, and molecular assays of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, endothelial nitric oxide synthase (eNOS), phospho-eNOS, and neural nitric oxide synthase (nNOS) in the penis. The effect of INF on HFD/STZ-induced diabetic ED and NADPH oxidase-mediated ROS generation was studied in diabetic corpus cavernosum. Untreated diabetic rats displayed significantly decreased erectile parameters, and increased plasma TNF-α levels, penile ROS production, p47(phox) and gp91(phox) expression compared with nondiabetic controls. INF neutralized TNF-α and significantly reduced ED in diabetic rats, in which marked decreases in p47(phox) and gp91(phox) expression and ROS generation in corpus cavernosum were noted. The ratio of phospho-eNOS to eNOS and expression of nNOS in the penis were significantly increased in INF-treated vs. untreated diabetic rats. Increased TNF-α expression associated with diabetes contributes to ED by promoting NAPDH oxidase-mediated ROS generation in corpus cavernosum. INF protects against diabetic ED by neutralizing TNF-α.

Long T ，Liu G ，Wang Y ，Chen Y ，Zhang Y ，Qin D ... -  《-》

RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction.

Bivalacqua TJ ，Champion HC ，Usta MF ，Cellek S ，Chitaley K ，Webb RC ，Lewis RL ，Mills TM ，Hellstrom WJ ，Kadowitz PJ ... -  《-》

Protective effect of exendin-4 treatment on erectile dysfunction induced by chronic methylglyoxal administration in rats.

The aim of this study was to investigate the effect of chronic exendin-4 (Ex-4) treatment on corpus cavernosum (CC) dysfunction in methylglyoxal (MGO) administered rats. Male rats were divided into four groups as control, MGO (75 mg/kg/day in drinking water for 12 weeks), MGO + low-dose Ex-4 (0.1 μg/kg twice daily subcutaneously for 12 weeks concomitant with MGO), and MGO + high-dose Ex-4 (1 μg/kg twice daily subcutaneously for 12 weeks concomitant with MGO). Nitric oxide (NO)-mediated endothelium-dependent and neurogenic CC relaxations were evaluated by acetylcholine (ACh) and electrical field stimulation (EFS), respectively. Apoptosis was determined by TUNEL. Endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), NADPH oxidase subunit gp91phox (NOX2), and Rho kinase (ROCK2) expressions in CC were investigated by immunohistochemistry. Levels of the malondialdehyde (MDA) and advanced oxidation protein products (AOPP) were also measured. In MGO administered rats, both endothelium-dependent and neurogenic CC relaxations were significantly impaired as compared to controls. Apoptotic cell death and levels of MDA and AOPP increased significantly in MGO administered rats. eNOS and p-eNOS expressions decreased significantly in MGO group, while gp91phox expressions increased significantly. The diminished relaxation in response to ACh or EFS as well as the changes in expression of proteins in MGO groups were significantly improved by exendin-4 treatment. TUNEL-positive cells, and levels of MDA and AOPP in MGO group rats were also significantly reduced by exendin-4. Exendin-4 treatment improves NO-mediated CC relaxations in MGO administered rats probably by inhibiting NADPH oxidase.

Dalaklioglu S ，Tasatargil A ，Kuscu N ，Celik S ，Celik-Ozenci C ，Ozdem S ，Barutcigil A ，Kucukcetin I ... -  《-》