title: Effect of lithium on endothelium-dependent and neurogenic relaxation of rat corpus cavernosum: role of nitric oxide pathway.
abstract: BACKGROUND
  Some studies have reported erectile dysfunction in patients receiving lithium through a mechanism that has not yet been defined. The aim of the present study was to verify the effect of acute lithium administration on the nonadrenergic noncholinergic (NANC)- and endothelium-mediated relaxation of rat isolated corpus cavernosum.
  
  
  METHODS
  The isolated rat corporeal strips were precontracted with phenylephrine hydrochloride (7.5 microM) and electrical field stimulation (EFS) was applied at different frequencies (2, 5, 10, and 15 Hz) to obtain NANC-mediated relaxation or relaxed by adding cumulative doses of acetylcholine (10nM-1mM) to obtain endothelium-dependent relaxation in the presence or absence of lithium (0.3, 0.5, 1, and 5mM). Also, effects of combining lithium (0.3mM) with 30 nM and 0.1 nM L-NAME (an NO synthase inhibitor) on NANC- and acetylcholine-mediated relaxation was investigated, respectively. Moreover, effects of combining lithium (1mM) with 0.1mM and 10 microM L-arginine (a precursor of NO) on NANC- and endothelium-mediated relaxation was assessed, respectively. Also, the effect of lithium (1mM) on relaxation to sodium nitroprusside (SNP; 1nM-1mM), an NO donor, was investigated.
  
  
  RESULTS
  The NANC-mediated relaxation was significantly (P<0.001) reduced by 1 and 5mM, but not by 0.3 and 0.5mM lithium. Lithium significantly (P<0.001) attenuated the maximum response to acetylcholine in a concentration-dependent manner. Combination of lithium (0.3mM) with 30 and 0.1 nM L-NAME, which separately had a minimum effect on NANC- and endothelium-mediated relaxation, significantly (P<0.001) reduced the NANC- and endothelium-mediated relaxation, respectively. Although L-arginine at 10 microM and 0.1mM did not alter the relaxant responses to acetylcholine and EFS, it improved the inhibition by lithium (1mM) of relaxant responses to acetylcholine and EFS, respectively. Also, SNP produced similar concentration-dependent relaxations from both groups.
  
  
  CONCLUSIONS
  Our experiments indicated that lithium likely by interfering with NO pathway in both endothelium and nitrergic nerve can result in impairment of both the endothelium- and NANC-mediated relaxation of rat corpus cavernosum.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Sadeghipour
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghasemi
authors.forename: Farzad
authors.initials: F
authors.lastname: Ebrahimi
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004558:Electric Stimulation; D004727:Endothelium / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010413:Penis / Q000187:drug effects* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D008094:Lithium; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester