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The kinin B1 receptor contributes to the cardioprotective effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in mice

Item Type:Article
Title:The kinin B1 receptor contributes to the cardioprotective effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in mice
Creators Name:Xu, J. and Carretero, O.A. and Shesely, E.G. and Rhaleb, N.E. and Yang, J.J. and Bader, M. and Yang, X.P.
Abstract:Recent studies have shown that inhibition of angiotensin-converting enzyme (ACE) or angiotensin II receptor causes up-regulation of the B1 receptor (B1R). Here we tested the hypothesis that activation of B1R partially contributes to the cardiac beneficial effect of ACE inhibitor (ACEi) and angiotensin II receptor blockers (ARB). B1R knockout mice (B1R-/-) and C57Bl/6J (wild-type controls, WT) were subjected to myocardial infarction (MI) by ligating the left anterior descending coronary artery. Three weeks after MI, each strain of mice was treated with vehicle, ACEi (ramipril, 2.5 mg/kg/day in drinking water) or ARB (valsartan, 40 mg/kg/day in drinking water) for 5 weeks. We found that 1) compared to WT mice, B1R-/- that underwent sham surgery had slightly but significantly increased LV diastolic dimension, LV mass and myocyte size, whereas SBP, cardiac function and collagen deposition did not differ between strains; 2) MI leads to LV hypertrophy, chamber dilatation and dysfunction similarly in both WT and B1R-/-; and 3) ACEi and ARB improved cardiac function and remodeling in both strains; however, these benefits were significantly diminished in B1R-/- mice. Our data suggest that kinins acting via the B1R participate in the cardioprotective effects of ACEi and ARB.
Keywords:Bradykinin, Heart, Receptor, Angiotensin II Type 1 Receptor Blockers, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Collagen, Animal Disease Models, Heart Rate, Left Ventricular Hypertrophy, Ligation, Inbred C57BL Mice, Knockout Mice, Myocardial Infarction, Cardiac Myocytes, Ramipril, Bradykinin B1 Receptor, Tetrazoles, Valine, Left Ventricular Dysfunction, Animals, Mice
Source:Experimental Physiology
ISSN:0958-0670
Publisher:Blackwell Publishing (U.K.)
Volume:94
Number:3
Page Range:322-329
Date:March 2009
Official Publication:https://doi.org/10.1113/expphysiol.2008.045583
PubMed:View item in PubMed

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