Treatments with losartan or enalapril are equally sensitive to deterioration in renal function from cyclooxygenase inhibition.
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.
Juhlin
Tord
T
Department of Cardiology, Malmö University Hospital, Malmö, Sweden.
Erhardt
Leif R
LR
Ottosson
Helene
H
Jönsson
Bo A G
BA
Höglund
Peter
P
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
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