Effect of indomethacin on the renal response to angiotensin II receptor blockade in healthy subjects.
BACKGROUND
Non-steroidal anti-inflammatory drugs are known to promote sodium retention and to blunt the blood pressure lowering effects of several classes of antihypertensive agents including beta-blockers, diuretics and angiotensin converting enzyme (ACE) inhibitors. The purpose of the present study was to investigate the acute and sustained effects of indomethacin on the renal response to the angiotensin II receptor antagonist valsartan and to the ACE inhibitor enalapril.


METHODS
Twenty normotensive subjects maintained on fixed sodium intake (100 mmol sodium/day) were randomized to receive for one week: valsartan 80 mg o.d., enalapril 20 mg o.d., valsartan 80 mg o.d. + indomethacin 50 mg bid and enalapril 20 mg o.d. + indomethacin 50 mg bid. This single-blind study was designed as a parallel (valsartan vs. enalapril) and cross-over trial (valsartan or enalapril vs. valsartan + indomethacin or enalapril + indomethacin). Renal hemodynamics and urinary electrolyte excretion were measured for six hours after the first and seventh administration of each treatment regimen.


RESULTS
The results show that valsartan and enalapril have comparable renal effects characterized by no change in glomerular filtration rate and significant increases in renal plasma flow and sodium excretion. The valsartan- and enalapril-induced renal vasodilation is not significantly blunted by indomethacin. However, indomethacin similarly abolishes the natriuresis induced by the angiotensin II antagonist and the ACE inhibitor.


CONCLUSIONS
This observation suggests that although angiotensin receptor antagonists do not affect prostaglandin metabolism, the administration of a non-steroidal anti-inflammatory drug blunts the natriuretic response to angiotensin receptor blockade.
Fricker
A F
AF
Division of Hypertension and Vascular Medicine, University Hospital, Lausanne, Switzerland.
Nussberger
J
J
Meilenbrock
S
S
Brunner
H R
HR
Burnier
M
M
D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018592:Cross-Over Studies; D004656:Enalapril / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects; D016037:Single-Blind Method; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013777:Tetrazoles; D004656:Enalapril; D000068756:Valsartan; D014633:Valine; D007213:Indomethacin