title: Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles.
abstract: OBJECTIVE
  We investigated the influence of sildenafil on cardiac contractility and diastolic relaxation and examined the distribution of phosphodiesterase-5 in the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine methyl ester (L-NAME).
  
  
  METHODS
  Male Wistar rats were treated with L-NAME and/or sildenafil for eight weeks. The Langendorff method was used to examine the effects of sildenafil on cardiac contractility and diastolic relaxation. The presence and location of phosphodiesterase-5 and phosphodiesterase-3 were assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA.
  
  
  RESULTS
  In isolated hearts, sildenafil prevented the reduction of diastolic relaxation (dP/dt) that was induced by L-NAME. In addition, phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial cells. The staining intensity was reduced by L-NAME, and sildenafil treatment abolished this reduction. Consistent with these results, the plasma levels of cGMP were decreased in the L-NAME-treated rats but not in rats that were treated with L-NAME + sildenafil.
  
  
  CONCLUSIONS
  The sildenafil-induced attenuation of the deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac myocytes is mediated (at least in part) by the inhibition of phosphodiesterase-5.
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, Unicamp, Campinas, São Paulo, Brazil.
authors.forename: Silvia Elaine
authors.initials: SE
authors.lastname: Ferreira-Melo
authors.forename: Caroline
authors.initials: C
authors.lastname: Demacq
authors.forename: Silvia
authors.initials: S
authors.lastname: Lacchini
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.forename: Maria Cláudia
authors.initials: MC
authors.lastname: Irigoyen
authors.forename: Heitor
authors.initials: H
authors.lastname: Moreno
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000097:blood / Q000378:metabolism; D003971:Diastole; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D019331:NG-Nitroarginine Methyl Ester