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CARDIOVASCULAR ANESTHESIOLOGY

Preservation of the Positive Lusitropic Effect of β-Adrenoceptors Stimulation in Diabetic Cardiomyopathy

Julien Amour, MD, PhD^*, Xavier Loyer, PhD, Pierre Michelet, MD, PhD, Aurélie Birenbaum, MD^*, Bruno Riou, MD, PhD, and Christophe Heymes, PhD

From the *UMPC Univ Paris 06, EA 3975, Département d'Anesthésie-Réanimation, Centre Hospitalier Universitaire (CHU) Pitié-Salpêtrière, Paris, France; INSERM U689, CHU Lariboisière, Université Denis Diderot - Paris 7, Paris, France; Service de Réanimation Chirurgicale, Hôpital Sainte-Maguerite, Université de la Méditerranée, Marseille, France; and UMPC Univ Paris 06, EA 3975, Service d'Accueil des Urgences, Centre Hospitalier Universitaire (CHU) Pitié-Salpêtrière, Paris, France.

Address correspondence and reprint requests to Dr. Julien Amour, Département d'Anesthésie-Réanimation, CHU Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75651 Paris cedex 13, France. Address e-mail to julien.amour{at}psl.aphp.fr.

Abstract

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 β-adrenoceptors stimulation could be altered, and β₃-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 β-adrenergic positive lusitropic effect is altered in diabetic cardiomyopathy, and that β₃-adrenoceptor over-expression is involved.

METHODS: β-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 β₃-adrenoceptor pathway inhibition by S-cyanopindolol (selective β₃-adrenoceptor antagonist) or by N^G-nitro-l-arginine-methyl-ester (nonselective nitric oxide synthase inhibitor) on the lusitropic response to isoproterenol (nonselective β-adrenoceptors agonist) was studied in vitro. Western blots were performed to quantify the protein expressions of β₁- and β₃-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 β-adrenoceptors stimulation was preserved in vivo (dobutamine) and in vitro (isoproterenol) in 4W and 12W diabetic, compared with healthy, rats. The β₃-adrenoceptor was up-regulated whereas β₁-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 β-adrenoceptor stimulation was preserved in diabetic cardiomyopathy. β₃-adrenoceptor over-expression does not seem to affect this process.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999