Document Detail

eNOS mediates L-arginine-induced inhibition of thick ascending limb chloride flux.
MedLine Citation:
PMID:  10642318     Owner:  NLM     Status:  MEDLINE    
We recently reported that the rat thick ascending limb (THAL) possesses an active isoform of nitric oxide synthase (NOS) that is substrate-limited in vitro. NO produced by THAL NOS inhibits chloride flux. Protein and transcript for each of the primary NOS isoforms-endothelial (eNOS), inducible (iNOS), and neuronal (nNOS)-have been demonstrated in THALs. However, the NOS isoform that mediates NO-induced inhibition of chloride flux is unknown. We hypothesized that NO produced from eNOS in the THAL inhibits NaCl transport. THALs from male eNOS, iNOS, and nNOS knockout mice and C57BL/6J wild-type controls were perfused in vitro and the response of transepithelial chloride flux (J(Cl)) to L-arginine (L-Arg), the substrate for NOS, and spermine NONOate (SPM), an NO donor was measured. We first tested whether isolated mouse THALs could synthesize NO and whether this NO inhibits transport. Addition of 0. 5 mmol/L L-Arg to the bath decreased J(Cl) from 105.8+/-17.5 to 79. 2+/-15.8 pmol/mm per minute (P<0.01) in C57BL/6J wild-type mice, whereas addition of D-Arginine had no effects on J(Cl.) In contrast, addition of 0.5 mmol/L L-Arg to the bath did not alter J(Cl) of THALs from eNOS knockout mice. When 10 micromol/L SPM was added to the bath of eNOS knockout THALs, J(Cl) decreased from 89.1+/-8.6 to 74.8+/-7.5 pmol/mm/min (P<0.05). Thus the lack of responsiveness of eNOS knockout THALs to L-Arg was not due to an inability to respond to NO. We next evaluated the role of iNOS and nNOS in the response to L-Arg. Addition of 0.5 mmol/L L-Arg to the bath decreased J(Cl) in THALs from iNOS and nNOS knockout mice by 37.7+/-6.4% (P<0.05) and 31.8+/-8.3% (P<0.01), respectively. We conclude that eNOS is the active isoform of NOS in the THAL under basal conditions. Mouse THAL eNOS responds to exogenous L-Arg by increasing NO production, which, in turn, inhibits J(Cl).
C F Plato; E G Shesely; J L Garvin
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  35     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-02-07     Completed Date:  2000-02-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  319-23     Citation Subset:  IM    
Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, MI 48202, USA.
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MeSH Terms
Arginine / pharmacology*
Biological Transport / drug effects,  genetics
Blood Pressure
Chlorides / metabolism*
Gene Expression Regulation, Enzymologic
Loop of Henle / enzymology*
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide / metabolism
Nitric Oxide Synthase / genetics*,  metabolism*
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Sodium / metabolism
Grant Support
Reg. No./Substance:
0/Chlorides; 10102-43-9/Nitric Oxide; 74-79-3/Arginine; 7440-23-5/Sodium; EC Oxide Synthase; EC Oxide Synthase Type II; EC Oxide Synthase Type III; EC protein, mouse; EC protein, mouse

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