Document Detail


Blood pressure responses to acute or chronic captopril in mice with disruption of bradykinin B2-receptor gene.
MedLine Citation:
PMID:  9488225     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To evaluate the role of kinins in the hypotensive response to angiotensin converting enzyme inhibition, we compared the blood pressure effects induced by acute or chronic captopril administration in a mouse strain (Bk2r-/-) with disruption of the bradykinin B2 receptor gene and in wild-type controls (J129 Sv mice). A second aim was to determine whether Icatibant, a selective bradykinin B2-receptor antagonist, prevented the blood pressure changes induced by acute captopril administration in Swiss, c57/B16, J129 Sv and Bk2r-/- mice. METHODS AND RESULTS: Under basal conditions, tail-cuff systolic blood pressure (SBP) and intra-arterial mean blood pressure (MBP) were higher in Bk2r-/- than in J129 Sv (SBP: 132+/-2 versus 113+/-3 mmHg; MBP: 144+/-6 versus 122+/-10 mmHg, P< 0.05 for both comparisons). Acute captopril administration (1 mg/kg body weight, intra-arterially) reduced the MBP of Bk2r-/- and J129 Sv by 36+/-8 and 31+/-7 mmHg, respectively. Swiss and c57/B16 mice showed similar decreases in MBP following captopril. Pretreatment with Icatibant (10 nmol/kg body weight, intra-arterially) did not influence the MBP responses to acute captopril in all the strains. Chronic administration of captopril (approximately 120 mg/kg body weight per day for 2 weeks in drinking water) reduced SBP in either Bk2r-/- or J129 Sv. The magnitude of this response was higher in Bk2r-/- than in J129 Sv (65+/-3 versus 47+/-4 mmHg, respectively, P < 0.01). CONCLUSIONS: Our results suggest that endogenous kinins do not participate in the hypotensive response to angiotensin converting enzyme inhibition in mice; in Bk2r-/-, the exaggerated blood pressure response to chronic captopril appears to be attributable to interference with unbalanced vasoconstrictor action of the renin-angiotensin system.
Authors:
C Emanueli; G R Angioni; V Anania; A Spissu; P Madeddu
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  15     ISSN:  0263-6352     ISO Abbreviation:  J. Hypertens.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-04-02     Completed Date:  1998-04-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1701-6     Citation Subset:  IM    
Affiliation:
Institute of Pharmacology, University of Sassari, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / administration & dosage,  pharmacology
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Animals
Blood Pressure / drug effects*
Bradykinin / administration & dosage,  analogs & derivatives,  pharmacology
Captopril / pharmacology*
Dose-Response Relationship, Drug
Drug Administration Routes
Gene Deletion*
Hypertension / metabolism,  physiopathology*
Male
Mice
Mice, Knockout / genetics
Receptor, Bradykinin B2
Receptors, Bradykinin / antagonists & inhibitors,  genetics,  physiology*
Vasoconstriction / drug effects
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Receptor, Bradykinin B2; 0/Receptors, Bradykinin; 130308-48-4/icatibant; 58-82-2/Bradykinin; 62571-86-2/Captopril

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


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