Document Detail


Inhibition of endopeptidase-24.15 decreases blood pressure in normotensive rats.
MedLine Citation:
PMID:  1889849     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The potent vasodilatory peptide bradykinin is cleaved at the Phe5-Ser6 bond in vitro by the metalloenzyme endopeptidase-24.15 (E.C.3.4.24.15). We now report that intravenous infusion of N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate, a specific active site-directed inhibitor of endopeptidase-24.15, produces an immediate drop in mean arterial pressure of as much as 50 mm Hg in pentobarbital-anesthetized, normotensive rats. Arterial pressure recovers within 5 minutes. The B2 bradykinin antagonist [Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin attenuates the decrease in mean arterial pressure resulting from treatment with the inhibitor. The endopeptidase-24.15 inhibitor potentiates the hypotensive effect of intravenous bradykinin infusion, increasing the maximal effect of the peptide by 47% and increasing the potency by almost 10-fold, while the response to intra-arterial bradykinin is less affected by the inhibitor. These results support a role for endopeptidase-24.15 in the inactivation of endogenous and exogenous bradykinin and suggest a direct involvement of the enzyme in the control of blood pressure.
Authors:
E M Genden; C J Molineaux
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  18     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1991 Sep 
Date Detail:
Created Date:  1991-10-11     Completed Date:  1991-10-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  360-5     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Mount Sinai School of Medicine, CUNY, NY 10029.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / physiology*
Bradykinin / analogs & derivatives,  antagonists & inhibitors,  pharmacology
Male
Metalloendopeptidases / antagonists & inhibitors*
Oligopeptides / pharmacology
Rats
Rats, Inbred Strains
Reference Values
Grant Support
ID/Acronym/Agency:
AM07420/AM/NIADDK NIH HHS; DA04218/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Oligopeptides; 103412-42-6/B 4162; 116560-97-5/N-(1-carboxy-3-phenylpropyl)-alanyl-alanyl-phenylalanine-4-aminobenzoate; 58-82-2/Bradykinin; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.15/thimet oligopeptidase
Comments/Corrections
Comment In:
Hypertension. 1991 Sep;18(3):366-71   [PMID:  1653769 ]

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


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