Critical blood pressure threshold dependence of hypertensive injury and repair in a malignant nephrosclerosis model Journal Article

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Authors: Griffin, K. A.; Polichnowski, A.; Litbarg, N.; Picken, M; Venkatachalam, M. A.; Bidani, A. K.
Article Title: Critical blood pressure threshold dependence of hypertensive injury and repair in a malignant nephrosclerosis model
Abstract: Most patients with essential hypertension do not exhibit substantial renal damage. Renal autoregulation by preventing glomerular transmission of systemic pressures has been postulated to mediate this resistance. Conversely, malignant nephrosclerosis (MN) has been postulated to develop when severe hypertension exceeds a critical ceiling. If the concept is valid, even modest blood pressure (BP) reductions to below this threshold regardless of antihypertensive class (1) should prevent MN and (2) lead to the healing of the already developed MN lesions. Both predicates were tested using BP radiotelemetry in the stroke-prone spontaneously hypertensive rats receiving 1% NaCl as drinking fluid for 4 weeks. Severe hypertension (final 2 weeks average systolic BP, 200 mm Hg) and MN (histological damage score 36+/-5; n=27) developed in the untreated stroke-prone spontaneously hypertensive rats but were prevented by all antihypertensive classes (enalapril [n=15], amlodipine [n=13], or a hydralazine/hydrochlorothiazide combination [n=15]) if the final 2-week systolic BP remained 190 mm Hg. More impressively, modest systolic BP reductions to 160 to 180 mm Hg (hydralazine/hydrochlorothiazide regimen) initiated at approximately 4 weeks in additional untreated rats after MN had already developed (injury score 35+/-4 in the right kidney removed before therapy) led to a striking resolution of the vascular and glomerular MN injury over 2 to 3 weeks (post-therapy left kidney injury score 9+/-2, P0.0001; n=27). Proteinuria also declined rapidly from 122+/-9.5 mg/24 hours before therapy to 20.5+/-3.6 mg 1 week later. These data clearly demonstrate the barotrauma-mediated pathogenesis of MN and the striking capacity for spontaneous and rapid repair of hypertensive kidney damage if new injury is prevented.
Journal Title: Hypertension
Volume: 64
Issue: 4
ISSN: 1524-4563; 0194-911X
Publisher: American Heart Association, Inc  
Date Published: 2014
Start Page: 801
End Page: 807
Language: ENG
DOI/URL:

10.1161/HYPERTENSIONAHA.114.03609
Notes: LR: 20151001; CI: (c) 2014; GR: DK-61653/DK/NIDDK NIH HHS/United States; GR: DK040426/DK/NIDDK NIH HHS/United States; GR: IK2 BX001285/BX/BLRD VA/United States; GR: R01 DK040426/DK/NIDDK NIH HHS/United States; JID: 7906255; 0 (Antihypertensive Agents); 0J48LPH2TH (Hydrochlorothiazide); 1J444QC288 (Amlodipine); 26NAK24LS8 (Hydralazine); 69PN84IO1A (Enalapril); NIHMS601302; OID: NLM: NIHMS601302; OID: NLM: PMC4162752; OTO: NOTNLM; 2014/06/23 [aheadofprint]; ppublish