Preservation of the positive lusitropic effect of β-adrenoceptors stimulation in diabetic cardiomyopathy

被引:18
作者
Amour, Julien [1 ]
Loyer, Xavier [2 ]
Michelet, Pierre [3 ]
Birenbaum, Aurelie [1 ]
Riou, Bruno [4 ]
Heymes, Christophe [2 ]
机构
[1] Univ Paris 06, Dept Anesthesie & Reanimat, CHU Pitie Salpetriere, UMPC,EA 3975, F-75651 Paris 13, France
[2] Univ Paris 07, INSERM, U689, CHU Lariboisiere, Paris, France
[3] Univ Aix Marseille 2, Serv Reanimat Chirurg, Hop St Maguerite, Marseille, France
[4] Univ Paris 06, Serv Accueil Urgences, CHU Pitie Salpetriere, UMPC,EA 3975, F-75651 Paris, France
关键词
D O I
10.1213/ane.0b013e3181806903
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
BACKGROUND: In diabetic cardiomyopathy, diastolic dysfunction results in part from sarcoplasmic reticulum abnormalities affecting both phospholamban and sarcoplasmic reticulum Ca2+ uptake (SERCA2a). Consequently, the positive lusitropic effect of beta-adrenoceptors stimulation could be altered, and beta(3)-adrenoceptor over-expression may play a role, as previously demonstrated with an altered positive inotropic effect. In this study, we tested the hypothesis that the beta(3)-adrenergic positive lusitropic effect is altered in diabetic cardiomyopathy, and that beta(3)-adrenoceptor over-expression is involved. METHODS: beta-adrenergic responses were investigated in vivo (dobutamine-echocardiography) and in vitro (papillary muscle preparation) in healthy and diabetic rats killed 4 (4W) and 12 (12W) wk after IV streptozotocin injection. The effect of beta(3)-adrenoceptor pathway inhibition by S-cyanopindolol (selective beta(3)-adrenoceptor antagonist) or by N-G-nitro-L-arginine-methyl-ester (nonselective nitric oxide synthase inhibitor) on the lusitropic response to isoproterenol (nonselective beta-adrenoceptors agonist) was studied in vitro. Western blots were performed to quantify the protein expressions of beta(1)- and beta(3)-adrenoceptors, phospholamban, and SERCA2a. Data are presented as mean percentages of baseline +/- SD. RESULTS: Despite the increased phospholamban/SERCA2a protein ratio and documented diastolic dysfunction, the positive lusitropic effect of beta-adrenoceptors stimulation was preserved in vivo (dobutamine) and in vitro (isoproterenol) in 4W and 12W diabetic, compared with healthy, rats. The beta(3)-adrenoceptor was upregulated whereas beta(1)-adrenoceptor was down-regulated in 4W and 12W diabetic, compared with healthy, rats. Nevertheless, S-cyanopindolol or N-G-nitro-L-arginine-methyl-ester had no lusitropic effect. CONCLUSIONS: The positive lusitropic effect of beta-adrenoceptor stimulation was preserved in diabetic cardiomyopathy. beta(3)-adrenoceptor over-expression does not seem to affect this process.
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收藏
页码:1130 / 1138
页数:9
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