title: The effects of cyclic guanylate cyclase stimulation on right ventricular hypertrophy and failure alone and in combination with phosphodiesterase-5 inhibition.
abstract: BACKGROUND
  We investigated if soluble guanylate cyclase stimulation either alone or in combination with phosphodiesterase-5 (PDE5) inhibition could prevent pressure overload-induced right ventricular (RV) hypertrophy and failure.
  
  
  METHODS
  The soluble guanylate cyclase stimulator BAY 41-2272 (BAY, 10 mg · kg⁻¹ · d⁻¹) either alone or in combination (BAY + SIL) with a PDE5 inhibitor sildenafil (SIL, 100 mg · kg⁻¹ · d⁻¹) was examined for prevention of RV hypertrophy and failure in Wistar rats (n = 73) operated by pulmonary trunk banding.
  
  
  RESULTS
  All treatments failed to inhibit the development of RV hypertrophy and failure. In the BAY and BAY + SIL groups, there was an increased mortality. Mean arterial blood pressure was lowered and cardiac output increased in the BAY + SIL group. Systolic RV pressure was increased in the BAY and BAY + SIL groups possibly because of an inotropic response and/or increased venous return.
  
  
  CONCLUSIONS
  Stimulation of soluble guanylate cyclase by BAY 41-2272 alone or in combination with sildenafil failed to prevent the development of RV hypertrophy and failure in rats subjected to pulmonary trunk banding. An increased mortality was observed in animals treated by BAY 41-2272 alone and in combination with sildenafil.
authors.affiliation: Department of Clinical Medicine, Cardiology (Research), Aarhus University Hospital, Aarhus, Denmark. asger.andersen@ki.au.dk
authors.forename: Asger
authors.initials: A
authors.lastname: Andersen
authors.forename: Jan M
authors.initials: JM
authors.lastname: Nielsen
authors.forename: Sarah
authors.initials: S
authors.lastname: Holmboe
authors.forename: Mads D
authors.initials: MD
authors.lastname: Vildbrad
authors.forename: Jens E
authors.initials: JE
authors.lastname: Nielsen-Kudsk
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D020536:Enzyme Activators / Q000009:adverse effects / Q000627:therapeutic use*; D006162:Guanylate Cyclase / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism; D000068677:Sildenafil Citrate; D000071756:Soluble Guanylyl Cyclase; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D020536:Enzyme Activators; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D011720:Pyrazoles; D011725:Pyridines; D018160:Receptors, Cytoplasmic and Nuclear; D013450:Sulfones; D000068677:Sildenafil Citrate; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP