Renoprotection by ACE inhibition or aldosterone blockade is blood pressure-dependent.
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 approximately 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.
Griffin
Karen A
KA
Department of Internal Medicine, Loyola University Medical Center, Maywood, IL 60153, USA. Martha.Prado@med.va.gov
Abu-Amarah
Isam
I
Picken
Maria
M
Bidani
Anil K
AK
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003692:Delayed-Action Preparations; D004656:Enalapril / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology / Q000517:prevention & control / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D016014:Linear Models; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D012965:Sodium Chloride / Q000008:administration & dosage; D013148:Spironolactone / Q000494:pharmacology*; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D003692:Delayed-Action Preparations; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D012965:Sodium Chloride; D004656:Enalapril