Zhou Ping, Wu Sheng-Ying, Yu Cheng-Fan, Wang Hua, Tang Chao-Shu, Lin Li, Yuan Wen-Jun
Cardiovascular Institute, First Hospital, Peking University, Beijing 100034.
Sheng Li Xue Bao. 2003 Aug 25;55(4):442-8.
To shed light on cardiac effects of the potent vasoconstrictive peptide urotensin II (U II), Langendorff-perfused isolated rat hearts were consecutively perfused with 0.1, 1 and 10 nmol/L U II, for 5 min at each dose, followed by 5-min washout. Moreover, isolated hearts subjected to 20-min global no-flow ischemia were reperfused with U II (1 or 10 nmol/L) for 20 min. Heart function parameters including heart rate, left ventricular pressure and dP/dt were monitored; content of protein and myoglobin, and activity of lactate dehydrogenase (LDH) in coronary effluent were determined; malondialdehyde (MDA) in myocardium and [(125)I]-U II binding sites in plasma membrane were measured after the completion of perfusion. The results showed that: (1) In normal rat hearts, the coronary flow was decreased and the heart function was suppressed by U II dose-dependently, and these changes were not abolished by washout. The leakage of cardiac protein, myoglobin and LDH increased with the increment of U II, but it diminished rapidly after washout. In contrast, MDA content in U II -treated myocardium was not statistically different from that in normal myocardium. (2) Ischemia-reperfusion caused significant decreases in coronary flow, suppression of heart function, and leakage of protein and LDH. In U II -reperfused hearts, all these disorders were significantly aggravated and myocardial MDA content significantly increased (P<0.01), to a greater extent in the presence of higher dose of U II. (3) The maximal binding capacity (B(max)) of U II receptors in plasma membrane from ischemia-reperfusion myocardium increased significantly as compared with that of normal myocardium (20.53+/-1.98 vs 14.65+/-1.78 fmol/mg pr, P<0.01), while Kd remained unchanged. These results indicate that U II caused injury to the isolated rat hearts under normal perfusion, and worsened the injury of the hearts under ischemia-reperfusion, in which U II receptors were up-regulated.
为了阐明强效血管收缩肽尾加压素II（U II）对心脏的影响，采用Langendorff灌流法对离体大鼠心脏进行实验，依次用0.1、1和10 nmol/L的U II灌流，每个剂量灌流5分钟，随后冲洗5分钟。此外，对经历20分钟全心无血流缺血的离体心脏用U II（1或10 nmol/L）再灌注20分钟。监测包括心率、左心室压力和dP/dt在内的心脏功能参数；测定冠状动脉流出液中蛋白质、肌红蛋白含量以及乳酸脱氢酶（LDH）活性；灌注结束后测定心肌中丙二醛（MDA）含量以及质膜中[（125）I]-U II结合位点。结果显示：（1）在正常大鼠心脏中，U II可使冠状动脉血流量减少，心脏功能受到剂量依赖性抑制，冲洗后这些变化并未消除。心脏蛋白质、肌红蛋白和LDH的漏出量随U II浓度增加而增加，但冲洗后迅速减少。相比之下，U II处理的心肌中MDA含量与正常心肌无统计学差异。（2）缺血再灌注导致冠状动脉血流量显著减少、心脏功能受抑制以及蛋白质和LDH漏出。在U II再灌注的心脏中，所有这些紊乱均显著加重，心肌MDA含量显著增加（P<0.01），且高剂量U II时增加幅度更大。（3）与正常心肌相比，缺血再灌注心肌质膜中U II受体的最大结合容量（B(max)）显著增加（20.53±1.98对14.65±1.78 fmol/mg pr，P<0.01），而解离常数（Kd）保持不变。这些结果表明，U II在正常灌注下可导致离体大鼠心脏损伤，并加重缺血再灌注时心脏的损伤，其中U II受体上调。
