Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease.
Although the angiotensin receptor antagonist (ARB) shares the angiotensin-II-blocking activity with the angiotensin-converting enzyme inhibitor (ACE-I), pharmacological mechanisms of action of these agents differ. We evaluated the temporal profiles of action of ACE-I and ARB on urinary protein excretion and nitrate/nitrate (NO(x)) excretion in hypertensive (140 and/or 90 mmHg) patients with chronic renal disease (serum creatinine < 265 (range, 44-265) micromol/l or creatinine clearance > 30 (range, 30-121) ml/min). Patients with mild (<1 g/day; range, 0.4-1.0) and moderate proteinuria (>1 g/day; range, 1.1-6.9) were randomly assigned to ACE-I- and ARB-treated groups, and were treated with ACE-I (trandolapril or perindopril) or ARB(losartan or candesartan) for 48 weeks. In all groups, treatment with ACE-I or ARB decreased blood pressure to the same level, but had no effect on creatinine clearance. In patients with mild proteinuria, neither ACE-I nor ARB altered urinary protein excretion. In patients with moderate proteinuria, ACE-I caused 44 +/- 6% reduction in proteinuria (from 2.7 +/- 0.5 to 1.5 +/- 0.4 g/day, n = 14) at 12 weeks, and this beneficial effect persisted throughout the protocol (48 weeks, 1.2 +/- 0.2 g/day). In contrast, ARB did not produce a significant decrease in proteinuria at 12 weeks (23 +/- 8%, n = 13), but a 41 +/- 6% reduction in proteinuria was observed at 48 weeks. Similarly, although early (12 weeks) increases in urinary NO(x) excretion were observed with ACE-I (from 257 +/- 70 to 1111 +/- 160 micromol/day) and ARB (from 280 +/- 82 to 723 +/- 86 micromol/day), the ARB-induced increase in NO(x) excretion was smaller than that by ACE-I (P < 0.05). In conclusion, although both ACE-I and ARB reduce blood pressure similarly, the effect of these agents on proteinuria differs in chronic renal disease with moderate proteinuria. Relatively early onset of the proteinuria-reducing effect was observed with ACE-I, which paralleled the increase in urinary NO(x) excretion. Conversely, ARB decreased proteinuria and increased urinary NO(x) excretion gradually. These time course-dependent changes in proteinuria and urinary NO(x) may reflect the pharmacological property of ACE-I and ARB, with regard to the action on bradykinin.
Matsuda
H
H
Ashikaga Red Cross Hospital, Tochigi, Japan.
Hayashi
K
K
Saruta
T
T
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D003404:Creatinine / Q000378:metabolism; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007564:Japan; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000652:urine; D011188:Potassium / Q000097:blood; D011507:Proteinuria / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D011897:Random Allocation; D011945:Receptors, Angiotensin / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013599:Systole / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D011945:Receptors, Angiotensin; D009569:Nitric Oxide; D003404:Creatinine; D011188:Potassium