Is the antiproteinuric effect of ACE inhibition mediated by interference in the renin-angiotensin system?
Angiotensin converting enzyme (ACE) inhibition causes specific renal effects, such as a rise in effective renal plasma flow, a fall in filtration fraction and a lowering of proteinuria. The mechanism of these renal effects is still debated. Recent animal studies suggest that non-angiotensin (Ang) II related actions of ACE inhibition, such as bradykinin accumulation, may have a role. We therefore investigated the effects of specific intervention in the renin-angiotensin system with the Ang II receptor antagonist losartan, and compared these effects to those obtained with ACE inhibition, as this comparison might resolve the question whether or not the effects of ACE inhibition are Ang II related. The effects of losartan and enalapril were studied in eleven patients with non-diabetic proteinuria and hypertension. The protocol consisted of seven periods, each lasting one month, in which patients received once daily placebo, 50 mg losartan, 100 mg losartan, placebo, 10 mg enalapril, 20 mg enalapril, and placebo, respectively. At the end of each study period proteinuria, blood pressure, and renal function were determined. On both doses of losartan and enalapril proteinuria and blood pressure fell, whereas ERPF increased and GFR remained stable. The fall in urinary protein excretion was similar for both drugs: 46.3% (28.3% to 63.1%) on 100 mg losartan versus 51.6% (37.0% to 69.2%) on 20 mg enalapril (expressed as Wilcoxon-based estimated median with 95% CI).(ABSTRACT TRUNCATED AT 250 WORDS)
Gansevoort
R T
RT
Department of Medicine, State University Hospital, Groningen, The Netherlands.
de Zeeuw
D
D
de Jong
P E
PE
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000502:physiology; D019808:Losartan; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D004656:Enalapril; D019808:Losartan