Document Detail

Temporal adjustment of the juxtaglomerular apparatus during sustained inhibition of proximal reabsorption.
MedLine Citation:
PMID:  10525054     Owner:  NLM     Status:  MEDLINE    
Tubuloglomerular feedback (TGF) stabilizes nephron function by causing changes in single-nephron GFR (SNGFR) to compensate for changes in late proximal flow (VLP). TGF responds within seconds and reacts over a narrow range of VLP that surrounds normal VLP. To accommodate sustained increases in VLP, TGF must reset around the new flow. We studied TGF resetting by inhibiting proximal reabsorption with benzolamide (BNZ; administered repeatedly over a 24-hour period) in Wistar-Froemter rats. BNZ acutely activates TGF, thereby reducing SNGFR. Micropuncture was performed 6-10 hours after the fourth BNZ dose, when diuresis had subsided. BNZ caused glomerular hyperfiltration, which was prevented with inhibitors of macula densa nitric oxide synthase (NOS). Because of hyperfiltration, BNZ increased VLP and distal flow, but did not affect the basal TGF stimulus (early distal salt concentration). BNZ slightly blunted normalized maximum TGF response and the basal state of TGF activation. BNZ sensitized SNGFR to reduction by S-methyl-thiocitrulline (SMTC) and caused the maximum TGF response to be strengthened by SMTC. Sensitization to type I NOS (NOS-I) blockers correlated with increased macula densa NOS-I immunoreactivity. Tubular transport measurements confirmed that BNZ affected TGF within the juxtaglomerular apparatus. During reduced proximal reabsorption, TGF resets to accommodate increased flow and SNGFR through a mechanism involving macula densa NOS.
S C Thomson; S Bachmann; M Bostanjoglo; C A Ecelbarger; O W Peterson; D Schwartz; D Bao; R C Blantz
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  104     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-11-16     Completed Date:  1999-11-16     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1149-58     Citation Subset:  AIM; IM    
Department of Medicine, Division of Nephrology/Hypertension, University of California School of Medicine, Veterans Affairs Medical Center, San Diego 92161, USA.
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MeSH Terms
Benzolamide / pharmacology
Glomerular Filtration Rate
Juxtaglomerular Apparatus / metabolism*
Kidney Tubules, Distal / metabolism
Kidney Tubules, Proximal / metabolism*
Loop of Henle / metabolism
Nitric Oxide Synthase / physiology
Nitric Oxide Synthase Type I
Rats, Wistar
Sodium Chloride / metabolism
Grant Support
Reg. No./Substance:
3368-13-6/Benzolamide; 7647-14-5/Sodium Chloride; EC Oxide Synthase; EC Oxide Synthase Type I; EC protein, rat
Comment In:
J Clin Invest. 1999 Oct;104(8):1007-9   [PMID:  10525035 ]

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