Re: Role of endothelin receptors and relationship with nitric oxide synthase in impaired erectile response in diabetic rats. Alkan E, Ugan RA, Basar MM, Halici Z, Karakus E, Balbay MD, Un H.Andrologia. 2016 May 4. doi: 10.1111/and.12607

Abstract

Read with great interest the article recently published entitled "Role of endothelin receptors and relationship with nitric oxide synthase in impaired erectile response in diabetic rats." by Alkan et al. in Andrologia (Alkan et al., 2017). The authors have examined the role of endothelin receptors and the relationship with nitric oxide synthase in impaired erectile response in diabetic rats. While endothelin-1 (ET-1), TNFα and iNOS gene expressions increased, erectile function decreased in the DM group compared to the healthy group at the end of the treatment with bosentan (BOS), an ET-1 receptor antagonist. eNOS, ET-RA and ET-RB gene expressions decreased in the DM group in a dose-dependent manner. The manuscript planned to evaluate the molecular mechanism of the protective effect of ET receptor antagonist on DM-induced ED. However, several methodological flaws hamper the overall quality of the experiment. Although the apomorphine test has been used to test erectile function, it would be better if in vitro organ bath was used for penile strips together with cavernosal nerve stimulation and intracavernosal pressure study to evaluate nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signalling pathway and cavernosal pressure measurement respectively (Liu et al., 2016; Martínez-Salamanca et al., 2016). Researchers should have assessed physiological muscle tone as an index to erectile function, that is intracavernosal pressure, assessment of nitric oxide production and cGMP levels which are better indicators of eNOS enzyme functions. The authors tested the preventative effect of BOS just after the onset of hyperglycaemia, but the therapeutic effect of ET-1 antagonist was not reported. It would be better if therapeutic group, 4 weeks after the injection of STZ, was used. The therapeutic group is important because erectile dysfunction is a complication of diabetes, and it requires time to develop. To test the therapeutic effect of an agent in DM, complications of DM must be established (Konturek et al., 2010; Usta et al., 2006). Recent studies have shown that increased oxidative stress and NOS uncoupling are accepted as a mechanistic link between erectile dysfunction and systemic endothelial dysfunction in type DM (Musicki & Burnett, 2017; Musicki, Hannan, Lagoda, Bivalacqua, & Burnett, 2016). But NOS uncoupling and penile ROS levels have not been evaluated in this study. Although neuropathic complications are common in DM, the NOS activity has not been investigated. It would be better if protein expressions were studied as these are better markers than gene expressions. Endothelial dysfunction in diabetes is characterised by a reduced nitric oxide bioavailability (Shi & Vanhoutte, 2017). There is no information in the literature about the protective role of ET-1 antagonist on oxidative stress, prevention of NOS uncoupling and NO bioavailability. It would be better to study these molecular tests. Furthermore, bosentan is a nonspecific ET-1 receptor antagonist. Bosentan cannot be used to assess effects on erectil...