title: Analysis of erectile responses to BAY 41-8543 and muscarinic receptor stimulation in the rat.
abstract: BACKGROUND
  Soluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) and in pathophysiologic conditions where NO formation or bioavailability is impaired, erectile dysfunction (ED) occurs.
  
  
  OBJECTIVE
  The aim of this study was to investigate erectile responses to the sGC stimulator BAY 41-8543 in physiologic and pathophysiologic conditions.
  
  
  METHODS
  Increases in intracavernosal pressure (ICP) in response to intracavernosal (ic) injections of BAY 41-8543 were investigated in the anesthetized rat.
  
  
  METHODS
  Increases in ICP/MAP in response to ic injections of BAY 41-8543 and the interaction of BAY 41-8543 with exogenous and endogenously released NO were investigated and the effect of the sGC stimulator on cavernosal nerve injury was assessed. The mechanism of the increase in ICP/MAP in response to ic injection of acetylcholine was investigated.
  
  
  RESULTS
  The ic injections of BAY 41-8543 increased ICP/MAP and the duration of the response. BAY 41-8543 was less potent than sodium nitroprusside (SNP) and ic injections of BAY 41-8543 and SNP produced a larger response than the algebraic sum of responses to either agent alone. Simultaneous ic injection of BAY 41-8543 and cavernosal nerve stimulation produced a greater response than either intervention alone. Atropine and cavernosal nerve crush injury decreased the response to nerve stimulation and ic injection of BAY 41-8543 restored the response.
  
  
  CONCLUSIONS
  These data show that BAY 41-8543 has significant erectile activity and can synergize with exogenous and endogenously released NO. This study shows that atropine and nerve crush attenuate the response to cavernosal nerve stimulation and that BAY 41-8543 can restore the response. The results with atropine, L-NAME and hexamethonium indicate that the response to ic injection of acetylcholine is mediated by muscarinic receptors and the release of NO with no significant role for nicotinic receptors. These results suggest that BAY 41-8543 would be useful in the treatment of ED.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112-2699, USA.
authors.forename: George F
authors.initials: GF
authors.lastname: Lasker
authors.forename: Edward A
authors.initials: EA
authors.lastname: Pankey
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Allain
authors.forename: Jasdeep S
authors.initials: JS
authors.lastname: Dhaliwal
authors.forename: Johannes-Peter
authors.initials: JP
authors.lastname: Stasch
authors.forename: Subramanyam N
authors.initials: SN
authors.lastname: Murthy
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D018679:Cholinergic Agonists / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D007267:Injections; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000294:innervation*; D059348:Peripheral Nerve Injuries; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C450679:BAY 41-8543; D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D009025:Morpholines; D018733:Nicotinic Antagonists; D020030:Nitric Oxide Donors; D010276:Parasympatholytics; D011743:Pyrimidines; D009599:Nitroprusside; D018738:Hexamethonium; D001285:Atropine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester