Role of endothelin receptors and relationship with nitric oxide synthase in impaired erectile response in diabetic rats

Andrologia. 2017 Mar;49(2). doi: 10.1111/and.12607. Epub 2016 May 4.

Abstract

To evaluate the protective role of bosentan (BOS), an endothelin-1 (ET-1) receptor antagonist, and to show the changes in rats with experimentally induced diabetic erectile dysfunction (ED), a total of 24 albino Wistar rats were allocated into four groups. Group 1 was the healthy group and Group 2 had diabetes mellitus (DM) induced by intraperitoneal injection of 60 mg kg-1 streptozotocin (STZ). Following the establishment of DM, Group 3 and Group 4 were treated with oral BOS doses of 50 mg kg-1 and 100 mg kg-1 , respectively, for 60 days. At the end of the treatment, we evaluated yawning and erection response to apomorphine treatment and then the animals were sacrificed. ET-1, eNOS, iNOS, tumour necrosis factor (TNF)-α, ET-RA and ET-RB mRNA expressions were analysed in cavernosal tissue. It was observed that yawning and erection response decreased in the diabetic group; however, both of these improved with BOS treatment. While ET-1, TNF-α and iNOS gene expressions increased, eNOS, ET-RA and ET-RB gene expressions decreased in the DM group compared to the healthy group. DM has a negative impact on cavernosal tissue blood flow through activating vasoconstrictor mediators in cavernosal tissue. BOS regulates significantly eNOS, iNOS and TNF-α expressions in a dose-dependent manner.

Keywords: Bosentan; diabetes mellitus; erectile dysfunction; rat.

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Bosentan
  • Diabetes Mellitus, Experimental / complications*
  • Dopamine Agonists / pharmacology
  • Endothelin Receptor Antagonists / administration & dosage
  • Endothelin Receptor Antagonists / therapeutic use*
  • Endothelin-1 / metabolism
  • Erectile Dysfunction / drug therapy*
  • Erectile Dysfunction / etiology*
  • Humans
  • Male
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Penile Erection / drug effects*
  • Penis / blood supply
  • Penis / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Endothelin A / metabolism
  • Receptor, Endothelin B / metabolism
  • Sulfonamides / administration & dosage
  • Sulfonamides / therapeutic use*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Dopamine Agonists
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • RNA, Messenger
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Sulfonamides
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos2 protein, rat
  • Nos3 protein, rat
  • Apomorphine
  • Bosentan