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Kinin B-1 receptor participates in the control of cardiac function in mice

机译：激肽B-1受体参与小鼠心功能的控制

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摘要

The kinins have an important role in control of the cardiovascular system. They have been associated with protective effects in the heart tissue. Kinins act through stimulation of two 7-transmembrane G protein-coupled receptors, denoted B-1 and 13, receptors. However, the physiological relevance of B receptor in the heart has not been clearly established. Using B-1 kinin receptor gene knock-out mice we tested the hypothesis that the B-1 receptor plays an important role in the control of baseline cardiac function. We examined the functional aspects of the intact heart and also in the isolated cardiomyocytes to study intracellular Ca2+ cycling by using confocal microscopy and whole-cell voltage clamp techniques. We measured heart rate, diastolic and systolic tension, contraction and relaxation rates and, coronary perfusion pressure. Whole-cell voltage clamp was performed to measure L-type Ca2+ current (I-Ca,I-L) The hearts from B-1(-/-) mice showed smaller systolic tension. The average values for WT and B-1(-/-) mice were 2.6 +/- 0.04 g vs. 1.6 +/- 0.08 g, respectively. This result can be explained, at least in part, by the decrease in the Ca2+ transient (3.1 +/- 0.06 vs. 3.4 +/- 0.09 for B and WT, respectively). There was an increase in I-Ca,I-L at depolarized membrane potentials. Interestingly, the inactivation kinetics of I-Ca,I-L was statistically different between the groups. The coronary perfusion pressure was higher in the hearts from B-1(-/-) mice indicating an increase in coronary resistance. This result can be explained by the significant reduction of eNOS (NOS-3) expression in the aorta of B-1(-/-) mice. Collectively, our results demonstrate that B-1 receptor exerts a fundamental role in the mammalian cardiac function. (c) 2007 Elsevier Inc. All rights reserved.
机译：激肽在控制心血管系统中具有重要作用。它们与心脏组织的保护作用有关。激肽通过刺激两个称为B-1和13的7个跨膜G蛋白偶联受体而起作用。但是，心脏中B受体的生理相关性尚未明确。使用B-1激肽受体基因敲除小鼠，我们测试了B-1受体在控制基线心脏功能中起重要作用的假设。我们通过使用共聚焦显微镜和全细胞电压钳技术研究了完整心脏以及分离的心肌细胞的功能方面，以研究细胞内Ca2 +循环。我们测量了心率，舒张压和收缩压，收缩和舒张率以及冠状动脉灌注压。进行全细胞电压钳测量L型Ca2 +电流（I-Ca，I-L）来自B-1（-/-）小鼠的心脏显示出较小的收缩压。 WT和B-1（-/-）小鼠的平均值分别为2.6 +/- 0.04 g和1.6 +/- 0.08 g。可以至少部分地通过减少Ca2 +瞬态来解释这一结果（B和WT分别为3.1 +/- 0.06与3.4 +/- 0.09）。在去极化膜电位下，I-Ca，I-L增加。有趣的是，两组间I-Ca，I-L的失活动力学在统计学上是不同的。 B-1（-/-）小鼠心脏中的冠状动脉灌注压更高，表明冠状动脉抵抗力增加。此结果可以通过B-1（-/-）小鼠主动脉中eNOS（NOS-3）表达的显着降低来解释。总的来说，我们的结果表明B-1受体在哺乳动物的心脏功能中起着基本作用。 （c）2007 Elsevier Inc.保留所有权利。

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