Rabelo E, De Angelis K, Bock P, Gatelli Fernandes T, Cervo F, Belló Klein A, Clausell N, Cláudia Irigoyen M
Laboratory of Cardiovascular Physiology, Department of Physiology, Basic and Health Science Institute, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegae.
Hypertension. 2001 Sep;38(3 Pt 2):576-80. doi: 10.1161/hy09t1.096185.
Adriamycin cardiotoxicity is associated with oxidative stress in the presence of globally depressed cardiac function. It is unknown if there is a similar profile with early diastolic changes and how it relates to baroreflex control of circulation. In this study, we evaluated baroreflex control of circulation in adriamycin-treated Wistar rats compared with controls, using invasive blood pressure recording processed by a data acquisition system (CODAS, 1 KHz). Baroreflex sensitivity was evaluated by modulating blood pressure with phenylephrine and sodium nitroprusside. Oxidative stress was quantified by chemiluminescence and by glutathione peroxidase enzyme activity. Diastolic dysfunction was characterized by increased left ventricle end-diastolic pressure in adriamycin-treated rats compared with controls with preserved ascending aortic flow. Baroreflex sensitivity in response to blood pressure elevation and reduction were similar in adriamycin (-2+/-0.27 and -3.19+/-0.56 bpm/mm Hg) and control rats (-1.35+/-0.15 and -2.52+/-0.39 bpm/mm Hg). Chemiluminescence was higher (20450+/-1286 versus 16517+/-1020 counts per second/mg protein) and glutathione peroxidase activity was lower (45.6+/-4.3 versus 76.4+/-6.9 micromol. min(-1). mg(-1) protein) in adriamycin rats compared with controls. Inverse correlations were observed between glutathione peroxidase activity and left ventricle end-diastolic pressure (r=-0.72, P=0.02), between baroreflex sensitivity to phenylephrine and left ventricle end-diastolic pressure (r=-0.77, P=0.004), and between chemiluminescence and baroreflex sensitivity to sodium nitroprusside (r=-0.75, P=0.02), whereas a positive correlation was observed between baroreflex sensitivity to sodium nitroprusside and glutathione peroxidase activity (r=0.7, P=0.04). Thus, adriamycin led to increased left ventricle end-diastolic pressure without changes in baroreflex sensitivity, and associated increased oxidative stress appeared to be related to reduction of reflex control of circulation.
阿霉素心脏毒性与心脏功能整体下降时的氧化应激有关。目前尚不清楚早期舒张期改变是否存在类似情况，以及它与压力反射对循环的控制有何关系。在本研究中，我们使用数据采集系统（CODAS，1千赫兹）处理的侵入性血压记录，评估了阿霉素处理的Wistar大鼠与对照组相比的压力反射对循环的控制。通过用去氧肾上腺素和硝普钠调节血压来评估压力反射敏感性。通过化学发光和谷胱甘肽过氧化物酶活性来量化氧化应激。与升主动脉血流保留的对照组相比，阿霉素处理的大鼠舒张功能障碍表现为左心室舒张末期压力升高。阿霉素组（-2±0.27和-3.19±0.56次/分钟/毫米汞柱）和对照组大鼠（-1.35±0.15和-2.52±0.39次/分钟/毫米汞柱）对血压升高和降低的压力反射敏感性相似。与对照组相比，阿霉素组大鼠的化学发光更高（20450±1286对16517±1020每秒计数/毫克蛋白质），谷胱甘肽过氧化物酶活性更低（45.6±4.3对76.4±6.9微摩尔·分钟-1·毫克-1蛋白质）。观察到谷胱甘肽过氧化物酶活性与左心室舒张末期压力之间呈负相关（r=-0.72，P=0.02），对去氧肾上腺素的压力反射敏感性与左心室舒张末期压力之间呈负相关（r=-0.77，P=0.004），化学发光与对硝普钠的压力反射敏感性之间呈负相关（r=-0.75，P=0.02），而对硝普钠的压力反射敏感性与谷胱甘肽过氧化物酶活性之间呈正相关（r=0.7，P=0.04）。因此，阿霉素导致左心室舒张末期压力升高而压力反射敏感性无变化，且相关的氧化应激增加似乎与循环反射控制的降低有关。
