Damasceno Denis D, Lima Mercia P, Motta Daisy F, Ferreira Anderson J, Quintão-Junior Judson F, Drummond Lucas R, Natali Antônio J, Almeida Alvair P, Pesquero Jorge L
Department of Educational Development, Federal Institute of Education, Science and Technology of Southeast Minas Gerais, Campus Barbacena, MG, Brazil.
Regul Pept. 2013 Feb 10;181:30-6. doi: 10.1016/j.regpep.2012.12.009. Epub 2013 Jan 11.
In order to understand the mechanisms of interaction between tonin-angiotensin and renin-angiotensin systems (RAS) we evaluated, "in vivo" and "in vitro", in Wistar rats, cardiovascular and electrocardiographic parameters after tonin administration. Arterial pressure (AP) and electrocardiogram (ECG) were recorded in awake animals before and after tonin administration. Langendorff technique was used to analyze cardiac function in isolated heart in the presence of tonin and video motion edge detection system was used to evaluate the effect of tonin upon contractile function of isolated rat ventricular cardiomyocytes. After tonin infusion rats presented significantly higher diastolic and mean arterial pressure (MAP) and heart rate (HR) as compared with control. The ECG analysis revealed shorter RR interval, increase in the low-frequency (LF) range of the heart rate variability (HRV) power (%) and decrease in the high-frequency (HF) of HRV power (%). Isolated hearts perfused with tonin presented an increase in the arterial coronary pressure (ACP) and decline in the ventricular systolic tension (ST), maximal (dT/dt+) and minimal (dT/dt) contractility. The rates of contraction and relaxation of isolated ventricular cardiomyocytes were significantly increased due to the presence of tonin. The angiotensin II (Ang II) levels in the coronary sinus effluent increased in the presence of tonin in a dose-dependent manner and the effect of tonin upon ACP was completely blocked by candesartan. Tonin is able to generate the vasoconstrictor peptide Ang II in the isolated heart of the rat and the cardiovascular response induced by tonin was completely blocked by candesartan, an indication that the action of Ang II on Ang II type 1 (AT1) receptors is the major mechanism of the heart effects. Tonin affects cardiomyocyte contractile function which may be due to interference with Ca(2+) handling.
为了了解托宁 - 血管紧张素与肾素 - 血管紧张素系统（RAS）之间的相互作用机制，我们在Wistar大鼠体内和体外评估了托宁给药后的心血管和心电图参数。在清醒动物给药前和给药后记录动脉压（AP）和心电图（ECG）。采用Langendorff技术分析托宁存在下离体心脏的心脏功能，并使用视频运动边缘检测系统评估托宁对离体大鼠心室心肌细胞收缩功能的影响。与对照组相比，托宁输注后大鼠的舒张压、平均动脉压（MAP）和心率（HR）显著升高。心电图分析显示RR间期缩短，心率变异性（HRV）功率低频（LF）范围增加，HRV功率高频（HF）范围降低。灌注托宁的离体心脏动脉冠状动脉压（ACP）升高，心室收缩张力（ST）、最大（dT/dt+）和最小（dT/dt）收缩力下降。由于托宁的存在，离体心室心肌细胞的收缩和舒张速率显著增加。托宁存在时，冠状窦流出液中的血管紧张素II（Ang II）水平呈剂量依赖性增加，坎地沙坦完全阻断了托宁对ACP的作用。托宁能够在大鼠离体心脏中产生血管收缩肽Ang II，坎地沙坦完全阻断了托宁诱导的心血管反应，这表明Ang II对1型血管紧张素II（AT1）受体的作用是心脏效应的主要机制。托宁影响心肌细胞收缩功能，这可能是由于干扰了Ca(2+)的处理。
