beta-Adrenergic activation reveals impaired cardiac calcium handling at early stage of diabetes.

@article{citeulike:1645725, abstract = {Cardiac function is known to be impaired in diabetes. Alterations in intracellular calcium handling have been suggested to play a pivotal role. This study aimed to test the hypothesis that beta-adrenergic activation can reveal the functional derangements of intracellular calcium handling of the 4-week diabetic heart. Langendorff perfused hearts of 4-week streptozotocin-induced diabetic rats were subjected to the beta-adrenoceptor agonist isoproterenol. Cyclic changes in [Ca(2+)](i) levels were measured throughout the cardiac cycle using Indo-1 fluorescent dye. Based on the computational analysis of the [Ca(2+)](i) transient the kinetic parameters of the sarcoplasmic reticulum Ca(2+)-ATPase and the ryanodine receptor were determined by minimizing the squared error between the simulated and the experimentally obtained [Ca(2+)](i) transient. Under unchallenged conditions, hemodynamic parameters were comparable between control and diabetic hearts. Isoproterenol administration stimulated hemodynamic function to a greater extent in control than in diabetic hearts, which was exemplified by more pronounced increases in rate of pressure development and decline. Under unchallenged conditions, [Ca(2+)](i) amplitude and rate of rise and decline of [Ca(2+)](i) as measured throughout the cardiac cycle were comparable between diabetic and control hearts. Differences became apparent under beta-adrenoceptor stimulation. Upon beta-activation the rate-pressure product showed a blunted response, which was accompanied by a diminished rise in [Ca(2+)](i) amplitude in diabetic hearts. Computational analysis revealed a reduced function of the sarcoplasmic reticulum Ca(2+)-ATPase and Ca(2+)-release channel in response to beta-adrenoceptor challenge. Alterations in Ca(2+)(i) handling may play a causative role in depressed hemodynamic performance of the challenged heart at an early stage of diabetes.}, address = {Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.}, author = {op den Buijs, J. and Mikl\'{o}s, Z. and van Riel, N. A. and Prestia, C. M. and Szenczi, O. and T\'{o}th, A. and Van der Vusse, G. J. and Szab\'{o}, C. and Ligeti, L. and Ivanics, T. }, citeulike-article-id = {1645725}, doi = {http://dx.doi.org/10.1016/j.lfs.2004.08.018}, issn = {0024-3205}, journal = {Life Sci}, keywords = {calcium, diabetes, heart, isoproterenol, rat, streptozotocin}, month = {January}, number = {10}, pages = {1083--1098}, posted-at = {2007-09-11 22:45:59}, priority = {0}, title = {beta-Adrenergic activation reveals impaired cardiac calcium handling at early stage of diabetes.}, url = {http://dx.doi.org/10.1016/j.lfs.2004.08.018}, volume = {76}, year = {2005} }

TY - JOUR ID - citeulike:1645725 L3 - citeulike-article-id:1645725 TI - beta-Adrenergic activation reveals impaired cardiac calcium handling at early stage of diabetes. JF - Life Sci VL - 76 IS - 10 SP - 1083 EP - 1098 AD - Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. SN - 0024-3205 N2 - Cardiac function is known to be impaired in diabetes. Alterations in intracellular calcium handling have been suggested to play a pivotal role. This study aimed to test the hypothesis that beta-adrenergic activation can reveal the functional derangements of intracellular calcium handling of the 4-week diabetic heart. Langendorff perfused hearts of 4-week streptozotocin-induced diabetic rats were subjected to the beta-adrenoceptor agonist isoproterenol. Cyclic changes in [Ca(2+)](i) levels were measured throughout the cardiac cycle using Indo-1 fluorescent dye. Based on the computational analysis of the [Ca(2+)](i) transient the kinetic parameters of the sarcoplasmic reticulum Ca(2+)-ATPase and the ryanodine receptor were determined by minimizing the squared error between the simulated and the experimentally obtained [Ca(2+)](i) transient. Under unchallenged conditions, hemodynamic parameters were comparable between control and diabetic hearts. Isoproterenol administration stimulated hemodynamic function to a greater extent in control than in diabetic hearts, which was exemplified by more pronounced increases in rate of pressure development and decline. Under unchallenged conditions, [Ca(2+)](i) amplitude and rate of rise and decline of [Ca(2+)](i) as measured throughout the cardiac cycle were comparable between diabetic and control hearts. Differences became apparent under beta-adrenoceptor stimulation. Upon beta-activation the rate-pressure product showed a blunted response, which was accompanied by a diminished rise in [Ca(2+)](i) amplitude in diabetic hearts. Computational analysis revealed a reduced function of the sarcoplasmic reticulum Ca(2+)-ATPase and Ca(2+)-release channel in response to beta-adrenoceptor challenge. Alterations in Ca(2+)(i) handling may play a causative role in depressed hemodynamic performance of the challenged heart at an early stage of diabetes. KW - calcium KW - diabetes KW - heart KW - isoproterenol KW - rat KW - streptozotocin AU - op den Buijs, J AU - Miklós, Z AU - van Riel, NA AU - Prestia, CM AU - Szenczi, O AU - Tóth, A AU - Van der Vusse, GJ AU - Szabó, C AU - Ligeti, L AU - Ivanics, T PY - 2005/01/21/ UR - http://dx.doi.org/10.1016/j.lfs.2004.08.018 ER -