L-arginine and tetrahydrobiopterin, but not sodium nitrite partially restored erectile dysfunction in aged rats

Aging Male. 2014 Dec;17(4):248-55. doi: 10.3109/13685538.2014.921150. Epub 2014 Jun 5.


Aging is associated with erectile dysfunction (ED), in which nitric oxide synthase (NOS) activity and NO bioavailability are reduced due to deficiencies of NOS cofactor (tetrahydrobiopterin, BH(4)) and substrate (L-arginine). We determined whether the prolonged treatment with sodium nitrite (NaNO(2)) as a storage form of NO ameliorates ED in aged rats. Male Sprague-Dawley rats were divided: younger, aged and NaNO(2)-treated (20 mg/kg per day) aged groups. The erectile (intracavernosal pressure [ICP]/mean arterial pressure [MAP]) and corpus cavernous (CC) responses were evaluated after 12 weeks. The ICP/MAP in aged rats was lower than in young controls, which was not improved by the NaNO(2) treatment. Immunohistochemical (IHC) staining for endothelial NOS and collagen deposition was performed. We assayed NO indirectly by measuring the level of its stable end products, nitrite/nitrate, using the Griess reagent. The relaxations to ACh and EFS in the aged group were considerably less than in the younger group, which were normalized by acute incubations of l-arginine or BH(4) of aged CC. In conclusion, NaNO(2) treatment did not restore erectile response while nitrate levels were enhanced in aged penis. The cofactor or substrate administrations, but not chronic exogenous modulation of NO system may be beneficial in aged men with ED.

Keywords: Aging; NaNO2 treatment; corpus cavernosum; erectile dysfunction; nitric oxide.

MeSH terms

  • Aging
  • Animals
  • Arginine / therapeutic use*
  • Biopterin / analogs & derivatives*
  • Biopterin / therapeutic use
  • Dose-Response Relationship, Drug
  • Erectile Dysfunction / drug therapy*
  • Male
  • Nitrates / analysis
  • Nitric Oxide Synthase Type III / analysis
  • Nitrites / analysis
  • Penile Erection / drug effects
  • Penis / chemistry
  • Penis / drug effects
  • Rats, Wistar
  • Sodium Nitrite / therapeutic use*


  • Nitrates
  • Nitrites
  • Biopterin
  • Arginine
  • Nitric Oxide Synthase Type III
  • sapropterin
  • Sodium Nitrite