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Lack of evidence of blood pressure-independent protection by renin-angiotensin system blockade after renal ablation.

Abstract：

BACKGROUND:The superiority of renin-angiotensin system (RAS) blockade in providing renoprotection has been attributed to class-specific blood pressure "(BP)-independent" mechanisms. However, the conventional BP measurement methodology on which such conclusions are based is inherently limited for an accurate assessment of the fluctuating ambient BP profiles. The present studies were undertaken to rigorously examine the relationship of renoprotection to the antihypertensive effects of RAS blockade using chronic BP radiotelemetry in the 5/6 renal ablation model. METHODS:Rats with 5/6 renal ablation received either no treatment, the angiotensin-converting enzyme inhibitor benazepril at a dose of 25, 50, and 100 mg/L; or the angiotensin receptor antagonist losartan at a dose of 50, 120, and 180 mg/L of drinking H2O; and were followed for seven weeks. RESULTS:Glomerulosclerosis (GS) at sacrifice (approximately 7 weeks) demonstrated a close correlation with the average systolic BP in untreated (r = 0.76, N = 20), benazepril-treated (r = 0.80, N = 33), losartan-treated (r = 0.83, N = 32), or all animals combined (r = 0.81, N = 85, P < 0.0001 for all correlations). The slope of the relationship between GS and BP (percentage of increase in GS/mm Hg increase in BP) in untreated rats (0.7 +/- 0.14) was not significantly altered by either benazepril (0.96 +/- 0.13) or losartan (0.60 +/- 0.08), indicating that RAS blockade, by either agent, resulted in renoprotection that was proportionate to the achieved BP reductions. CONCLUSIONS:These data demonstrate that RAS blockade provides renoprotection in the rat remnant kidney model of progressive GS, primarily through "BP-dependent" and not "BP-independent" mechanisms.

journal_name

Kidney Int

journal_title

Kidney international

authors

Bidani AK,Griffin KA,Bakris G,Picken MM

doi

10.1046/j.1523-1755.2000.00009.x

subject

Has Abstract

pub_date

2000-04-01 00:00:00

pages

1651-61

issue

4

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)46914-5

journal_volume

57

pub_type

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