Document Detail

Renal effects of concurrent E-24.11 and ACE inhibition in the aorto-venocaval fistula rat.
MedLine Citation:
PMID:  8922744     Owner:  NLM     Status:  MEDLINE    
1. The present studies compare the early renal response to (a) an endopeptidase-24.11 (E-24.11) inhibitor (candoxatrilat) (b) an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) and (c) the combination of endopeptidase-24.11 and ACE inhibition in the rat A-V fistula model of chronic volume overload. 2. Candoxatrilat (3 and 10 mg kg-1) i.v. produced a prompt 3 fold increase in urinary sodium and cyclic GMP excretion without affecting significantly blood pressure or glomerular filtration rate (GFR). 3. Lisinopril (0.03 mg kg-1) alone inhibited the pressor response to angiotensin I but had no significant effect on urinary sodium excretion or blood pressure. 4. Lisinopril (0.03 mg kg-1) attenuated significantly the early natriuretic response to candoxatrilat (3 mg kg-1) and the associated rise in urinary cyclic GMP, but sodium excretion eventually reached levels associated with acute E-24.11 inhibition. 5. Doses of the dual E-24.11/ACE inhibitor, sampatrilat, that inhibited the pressor response to angiotensin I reduced mean arterial blood pressure and produced a delayed natriuresis and rise in urinary cyclic GMP excretion when compared to candoxatrilat alone. 6. Concurrent administration of an ACE inhibitor reduces the early renal response to E-24.11 inhibition in the A-V fistula rat, an effect attributable to the hypotensive action of this combination.
J E Kirk; M R Wilkins
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  119     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1996 Nov 
Date Detail:
Created Date:  1997-03-10     Completed Date:  1997-03-10     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  943-8     Citation Subset:  IM    
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
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MeSH Terms
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Arteriovenous Fistula / physiopathology*
Kidney / drug effects*,  physiopathology
Lisinopril / pharmacology
Natriuresis / drug effects*
Neprilysin / pharmacology*
Rats, Wistar
Venae Cavae*
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 83915-83-7/Lisinopril; EC

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