title: Treatments with losartan or enalapril are equally sensitive to deterioration in renal function from cyclooxygenase inhibition.
abstract: BACKGROUND
  The beneficial effects of angiotensin converting enzyme (ACE)-inhibitors are in part mediated through the inhibition of the degradation of the vasodilator bradykinin. The bradykinin effect is counteracted by cyclooxygenase-inhibitors. Angiotensin receptor blockers (ARBs) do not affect bradykinin.
  
  
  OBJECTIVE
  To test the hypothesis that renal counteraction from a cyclooxygenase-inhibitor, diclofenac, is different in subjects treated with an ACE-inhibitor, enalapril compared with an ARB, losartan.
  
  
  METHODS
  Twelve elderly, healthy, slightly over-hydrated subjects received diclofenac orally after pre-treatment with a diuretic, bendroflumethiazide, and enalapril or bendroflumethiazide and losartan, in a double-blind cross-over fashion, with a wash-out period of at least 1 week.
  
  
  RESULTS
  Diclofenac reduced GFR significantly from 81(64-98) ml/min at first observations after dose for enalapril to 29(16-42) and from 76(64-88) after losartan to 35(24-46). There was no significant difference between enalapril and losartan in GFR. Diclofenac induced decreases in urine flow, excretion rates and clearances of sodium, osmolality clearance and free water clearance, irrespective of treatment with enalapril or losartan. However, serum potassium and handling of potassium were significantly lower after losartan-treatment.
  
  
  CONCLUSIONS
  The negative renal effects of diclofenac administration in subjects with activation of the renin-angiotensin system and enalapril treatment are the same in subjects with activation of the renin-angiotensin system and losartan treatment.
authors.affiliation: Department of Cardiology, Malmö University Hospital, Malmö, Sweden.
authors.forename: Tord
authors.initials: T
authors.lastname: Juhlin
authors.forename: Leif R
authors.initials: LR
authors.lastname: Erhardt
authors.forename: Helene
authors.initials: H
authors.lastname: Ottosson
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
authors.forename: Peter
authors.initials: P
authors.lastname: Höglund
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001920:Bradykinin / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D004008:Diclofenac / Q000009:adverse effects*; D004232:Diuretics / Q000494:pharmacology / Q000627:therapeutic use; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D004232:Diuretics; D004008:Diclofenac; D004656:Enalapril; D019808:Losartan; D001920:Bradykinin