Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease

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Abstract
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 (NOx) excretion in hypertensive (140 and/or 90 mmHg) patients with chronic renal disease (serum creatinine30 (range, 30–121) ml/min). Patients with mild (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 446% reduction in proteinuria (from 2.70.5 to 1.50.4 g/day, n=14) at 12 weeks, and this beneficial effect persisted throughout the protocol (48 weeks, 1.20.2 g/day). In contrast, ARB did not produce a significant decrease in proteinuria at 12 weeks (238%, n=13), but a 416% reduction in proteinuria was observed at 48 weeks. Similarly, although early (12 weeks) increases in urinary NOx excretion were observed with ACE-I (from 25770 to 1111160 mol/day) and ARB (from 28082 to 72386 mol/day), the ARB-induced increase in NOx excretion was smaller than that by ACE-I (Px excretion. Conversely, ARB decreased proteinuria and increased urinary NOx excretion gradually. These time course-dependent changes in proteinuria and urinary NOx may reflect the pharmacological property of ACE-I and ARB, with regard to the action on bradykinin.

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