Document Detail

Nitric oxide release as an essential mitigating step in tubuloglomerular feedback: observations during intrarenal nitric oxide clamp.
MedLine Citation:
PMID:  9727367     Owner:  NLM     Status:  MEDLINE    
Nitric oxide synthase inhibition in the kidney enhances tubuloglomerular feedback (TGF) responsiveness. This may reflect either the effect of reduced basal nitric oxide (NO) availability or the effect of impaired NO release that is physiologically induced by TGF activation. However, it is unknown whether the latter actually takes place. In this study, it was hypothesized that NO is released (from macula densa cells or endothelium) as part of the normal TGF loop, and mitigates the TGF response. In Sprague Dawley rats, TGF responsiveness was assessed (fall in tubular stop flow pressure, deltaSFP, upon switching loop of Henle perfusion rates from 0 to 40 nl/min) during an intrarenal NO clamp (systemic infusion of nitro-L-arginine, 10 microg/kg per min, followed by intrarenal nitroprusside infusion adjusted to restore renal blood flow [RBF]). This maneuver was presumed to fix intrarenal NO impact at a physiologic level. To validate the approach, TGF responsiveness during an intrarenal angiotensin II (AngII) clamp (systemic infusion of enalaprilat 0.2 mg/kg per min, followed by intrarenal AngII infusion) was also studied. AngII is presumed to modulate but not mediate, TGF, thus not to increase as part of the TGF loop. In untreated animals, RBF was 7.4 +/- 0.4 ml/min, and deltaSFP was 5.7 +/- 1.6 mmHg. Nitro-L-arginine infusion alone reduced RBF to 5.3 +/- 0.5 ml/min (P < 0.05); with nitroprusside infusion, RBF was restored to 8.3 +/- 0.7 ml/min. In this condition (NO clamp), deltaSFP was markedly increased to 19.6 +/- 3.2 mmHg (P < 0.05). By contrast, deltaSFP, which was virtually abolished during enalaprilat alone (0.2 +/- 0.3 mmHg), was not significantly different from controls during AngII clamp (8.2 +/- 1.0 mmHg). These data suggest that NO may well be released upon TGF activation. By contrast, AngII is not dynamically involved in TGF activation, but may modulate the TGF response. Thus, dynamic release of NO during TGF activation mitigates the TGF response, so that it will offset the action of a primary, as yet undefined, vasoconstrictor mediator. The source of this NO, macula densa or endothelium, remains to be elucidated.
E Turkstra; B Braam; H A Koomans
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  9     ISSN:  1046-6673     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-12-09     Completed Date:  1998-12-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1596-603     Citation Subset:  IM    
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
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MeSH Terms
Analysis of Variance
Angiotensin II / administration & dosage,  metabolism*
Angiotensin-Converting Enzyme Inhibitors
Disease Models, Animal
Enalapril / pharmacology
Enzyme Inhibitors / pharmacology
Glomerular Filtration Rate / drug effects
Kidney Glomerulus / drug effects,  secretion*
Kidney Tubules / drug effects,  secretion*
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / metabolism*
Nitric Oxide Synthase / antagonists & inhibitors
Pressoreceptors / physiology
Rats, Sprague-Dawley
Reference Values
Renal Circulation / drug effects
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Enzyme Inhibitors; 10102-43-9/Nitric Oxide; 11128-99-7/Angiotensin II; 50903-99-6/NG-Nitroarginine Methyl Ester; 75847-73-3/Enalapril; EC Oxide Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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