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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice
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Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice

机译：组织激肽释放酶缺陷小鼠的血压正常与心血管异常

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摘要

Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins in many organs like the kidneys. colon. salivary glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans, but the exact role of the protease in cardiovascular function has not been established largely because of the lack of specific inhibitors. This study demonstrates that mice lacking tissue kallikrein are unable to generate significant levels of kinins in most tissues and develop cardiovascular abnormalities early in adulthood despite normal blood pressure. The heart exhibits septum and posterior wall thinning and a tendency to dilatation resulting in reduced left ventricular mass. Cardiac function estimated in vivo and in vitro is decreased both under basal conditions and in response to p- adrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in isolated perfused carotid arteries. which express, like the heart, low levels of the protease. These data show that tissue kallikrein is the main kinin-generating enzyme in vivo and that a functional kallikrein--kinin system is necessary for normal cardiac and arterial function in the mouse. They suggest that the kallikrein--kinin system could be involved in the development or progression of cardiovascular diseases.
机译：组织激肽释放酶是一种丝氨酸蛋白酶，被认为与肾脏等许多器官的生物活性肽激肽的产生有关。结肠。唾液腺，胰腺和血管。低肾合成和组织激肽释放酶的尿排泄已反复与动物和人类的高血压有关，但是由于缺乏特异性抑制剂，蛋白酶在心血管功能中的确切作用尚未得到明确。这项研究表明，尽管血压正常，但缺乏激肽释放酶组织的小鼠在大多数组织中均无法产生显着水平的激肽，并且在成年早期无法形成心血管异常。心脏的中隔和后壁变薄，并有扩张的趋势，导致左心室重量减少。在基础条件下以及对β-肾上腺素能刺激的响应下，体内和体外估计的心脏功能均降低。此外，在孤立的灌注颈动脉中血流诱导的血管舒张受损。像心脏一样表达低水平的蛋白酶。这些数据表明组织激肽释放酶是体内主要激肽生成酶，功能性激肽释放酶-激肽系统对于小鼠的正常心脏和动脉功能是必需的。他们认为激肽释放酶-激肽系统可能与心血管疾病的发生或发展有关。

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