Inhibition of inducible nitric oxide synthase improved erectile dysfunction in rats with type 1 diabetes

Andrologia. 2021 Sep;53(8):e14138. doi: 10.1111/and.14138. Epub 2021 Jun 16.


Diabetes mellitus (DM), which is closely related to microvascular dysfunction, is a risk factor for erectile dysfunction (ED). Furthermore, the upregulation of inducible nitric oxide synthase (iNOS) is associated with systemic vascular dysfunction in rats with diabetes. The purpose of this study was to investigate the role of iNOS in diabetes mellitus erectile dysfunction (DMED). First, we developed a type 1 DM rat model using streptozotocin and selected those that developed DMED. Then, we injected these rats with the 1400W, an iNOS inhibitor, for 10 weeks and subsequently assessed their ED. Lastly, we performed various molecular studies and histopathological analyses of penile tissues collected from these rats after the experiments. Through the histopathological studies, we also found that the treatment restored the ratios of the smooth muscle to collagen fibres, delayed the development of microvascular injury and alleviated the oxidative stress caused by hyperglycaemia. Based on these results, we confirmed that upregulation of iNOS leads to microvascular dysfunction in patients with ED. Overall, we found that inhibition of iNOS displayed beneficial effects in the treatment of ED, suggesting that its mechanism should be further explored.

Keywords: diabetes mellitus; erectile dysfunction; inducible-nitric oxide synthase.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Type 1* / complications
  • Erectile Dysfunction* / drug therapy
  • Erectile Dysfunction* / etiology
  • Male
  • Nitric Oxide
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / metabolism*
  • Penile Erection
  • Penis / metabolism
  • Rats


  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat