Document Detail

Diminished cardioprotective response to inhibition of angiotensin-converting enzyme and angiotensin II type 1 receptor in B(2) kinin receptor gene knockout mice.
MedLine Citation:
PMID:  11375278     Owner:  NLM     Status:  MEDLINE    
Using B(2) kinin receptor gene knockout mice (B(2)(-/-)), we tested the hypothesis that (l) lack of B(2) receptors may affect blood pressure and cardiac function and aggravate cardiac remodeling after myocardial infarction (MI), and (2) kinins partially mediate the cardiac beneficial effect of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II type 1 receptor antagonists (AT(1)-ant), whereas lack of B(2) receptors may diminish this cardioprotective effect. Chronic heart failure (HF) was induced by MI, which was caused by coronary artery ligation in both B(2)(-/-) and 129/SvEvTac mice (wild-type control, B(2)(+/+)). An ACEi (ramipril, 2.5 mg/kg/d) or AT(1)-ant (L-158809, 3 mg/kg/d) was given 1 week after MI and was continued for 12 weeks. Left ventricular (LV) ejection fraction, cardiac output (CO), diastolic LV dimension (LVDd), and LV mass were evaluated by echocardiography. Myocyte cross-sectional area and interstitial collagen fraction were studied histopathologically. We found that basal blood pressure and cardiac function were similar in B(2)(+/+) and B(2)(-/-) mice. After MI, development of HF and remodeling were also similar between the 2 strains. The ACEi improved cardiac function and remodeling in both strains; however, its effects were attenuated in B(2)(-/-) mice (respective values for B(2)(+/+) versus B(2)(-/-) mice: overall increase in ejection fraction, 64+/-10% versus 21+/-5% [P<0.01]; increase in CO, 69+/-17% versus 23+/-9% [P<0.01]; overall decrease in LVDd, -24+/-3% versus -7+/-4% [P<0.01]; and decrease in LV mass, -38+/-3% versus -6+/-6% [P<0.01]). AT(1)-ant had a beneficial cardiac effect similar to that produced by ACEi, and this effect was also diminished in B(2)(-/-) mice (respective values for B(2)(+/+) versus B(2)(-/-) mice: overall increase in ejection fraction, 46+/-10% versus 25+/-9% [P<0.01]; increase in CO, 44+/-14% versus 15+/-5% [P<0.01]; overall decrease in LVDd, -14+/-4% versus -6+/-3% [P<0.01]; and decrease in LV mass, -33+/-4 versus -16+/-7% [P<0.01]). The effect of ACEi or AT(1)-ant on myocyte cross-sectional area was similar between strains; however, their effect on the interstitial collagen fraction was diminished in B(2)(-/-) mice. We concluded that (1) lack of B(2) kinin receptors does not affect cardiac phenotype or function, either under normal physiological conditions or during the development of HF; and (2) kinins acting via the B(2) receptor play an important role in the cardioprotective effect of ACEi and AT(1)-ant.
X P Yang; Y H Liu; D Mehta; M A Cavasin; E Shesely; J Xu; F Liu; O A Carretero
Related Documents :
161478 - Echocardiographic evaluation of the effect of hemodialysis on cardiac size and function...
1838248 - Function and structure of the failing left ventricular myocardium in aortic valve disea...
12461318 - Enhanced external counterpulsation as treatment for chronic angina in patients with lef...
23960698 - The fate of post-myocardial infarction thrombi.
3436358 - Verapamil in a new model of severe local myocardial ischaemia due to combined coronary ...
21278798 - Changes in echocardiographic measures of systolic and diastolic function in children 1 ...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  88     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-05-25     Completed Date:  2001-06-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1072-9     Citation Subset:  IM    
Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Antihypertensive Agents / pharmacology
Blood Pressure / drug effects
Collagen / metabolism
Cytoprotection / drug effects,  physiology*
Disease Models, Animal
Disease Progression
Enzyme Inhibitors / pharmacology
Heart Failure / etiology,  genetics,  pathology
Heart Function Tests / drug effects
Imidazoles / pharmacology
Mice, Inbred Strains
Mice, Knockout
Myocardial Infarction / complications,  metabolism*,  pathology
Myocardium / metabolism,  pathology
Ramipril / pharmacology
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptor, Bradykinin B2
Receptors, Angiotensin / antagonists & inhibitors*
Receptors, Bradykinin / deficiency*,  genetics
Tetrazoles / pharmacology
Ventricular Remodeling / drug effects,  genetics
Grant Support
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Enzyme Inhibitors; 0/Imidazoles; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Receptor, Bradykinin B2; 0/Receptors, Angiotensin; 0/Receptors, Bradykinin; 0/Tetrazoles; 135145-96-9/L 158809; 87333-19-5/Ramipril; 9007-34-5/Collagen

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

Previous Document:  ADAR1 is involved in the development of microvascular lung injury.
Next Document:  Exaggerated left ventricular dilation and reduced collagen deposition after myocardial infarction in...