on January 6, 2003
Published online before print January 6, 2003, doi: 10.1161/01.HYP.0000049881.25304.73
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Submitted on August 12, 2002
From the Departments of Internal Medicine (K.A.G., I.A.-A., A.K.B.) and Pathology (M.P.), Loyola University Medical Center, Maywood, Ill, and Edward Hines Jr Hospital, Hines, Ill. * To whom correspondence should be addressed. E-mail: Martha.Prado{at}med.va.gov.
Abstract—Renin-angiotensin-aldosterone system blockade has been shown to protect against renal damage in salt-supplemented, stroke-prone spontaneously hypertensive rats (SHRsp). Based on intermittent tail-cuff blood pressure (BP) measurements, it has been claimed that such protection is BP-independent and mediated by a blockade of the direct tissue-damaging effects of angiotensin and/or aldosterone. BP radiotelemetry was performed for 8 weeks in
Revised on August 28, 2002
Renoprotection by ACE Inhibition or Aldosterone Blockade Is Blood Pressure-Dependent
Karen A. Griffin*;
10-week-old male SHRsp who received a standard diet and either tap water (n=10) or 1% NaCl to drink. Saline-drinking SHRsp were either left untreated (n=12), received enalapril (50 mg/L) in drinking fluid (n=9), or had subcutaneous implantation of time-release 200-mg pellets of aldactone (n=10). The average systolic BP (mean±SEM) during the final 3 weeks was significantly higher (P<0.05) in untreated saline-drinking (215±6 mm Hg) SHRsp but not aldactone-treated (198±4 mm Hg) or enalapril-treated treated SHRsp (173±1 mm Hg), as compared with tap water-drinking SHRsp (197±3 mm Hg). Histological renal damage scores at 8 weeks paralleled the BP in all groups, with an excellent correlation (r=0.8, P<0.001, n=41). Moreover, a renal damage score of >5 was only observed in SHRsp whose average systolic BP during the final 3 weeks exceeded 200 mm Hg, indicating a threshold relation with BP. These data show that protection by renin-angiotensin-aldosterone system blockade in this model is BP-dependent and mediated by preventing the severe increases in BP seen in untreated salt-supplemented SHRsp and further underscore the limitations of interpretations based on conventional tail-cuff BP measurements.
Key words: hypertension, renal • rats, stroke-prone SHR • nephrosclerosis • autoregulation
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