Circulating angiotensin II deteriorates left ventricular function with sympathoexcitation via brain angiotensin II receptor.
Circulating angiotensin II deteriorates left ventricular function with sympathoexcitation via brain angiotensin II receptor.
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DOI：
10.14814/phy2.12514
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发表时间：
2015-08
影响因子：
2.5
通讯作者：
Sunagawa K
中科院分区：
文献类型：
--
作者：
Shinohara K;Kishi T;Hirooka Y;Sunagawa K
交感神经兴奋有助于心力衰竭的进展。脑血管紧张素II型1受体（AT1R）的激活引起中枢交感神经兴奋。因此，我们评估了一种假设，即与心力衰竭模型中报道的相比，循环血管紧张素II的增加通过激活大脑中的AT1R通过中枢交感神经兴奋影响心功能。在Sprague-Dawley大鼠中，皮下输注血管紧张素II 14天可增加循环血管紧张素II水平，与心肌梗死后心力衰竭模型大鼠的水平相当。与对照组相比，血管紧张素II输注增加了24小时尿去甲肾上腺素排泄量和收缩压。血管紧张素II输注使左心室（LV）肥大，但不改变腔室尺寸，同时增加舒张末期压。左室压力-容积关系显示血管紧张素II对收缩末期弹性无影响，但明显增加舒张末期弹性。慢性脑室内输注AT1R阻滞剂氯沙坦可减轻这些血管紧张素ii诱导的变化。综上所述，心衰时循环血管紧张素II能够部分通过脑内AT1R诱导交感神经兴奋，从而导致左室舒张功能障碍。
Sympathoexcitation contributes to the progression of heart failure. Activation of brain angiotensin II type 1 receptors (AT1R) causes central sympathoexcitation. Thus, we assessed the hypothesis that the increase in circulating angiotensin II comparable to that reported in heart failure model affects cardiac function through the central sympathoexcitation via activating AT1R in the brain. In Sprague-Dawley rats, the subcutaneous infusion of angiotensin II for 14 days increased the circulating angiotensin II level comparable to that reported in heart failure model rats after myocardial infarction. In comparison with the control, angiotensin II infusion increased 24 hours urinary norepinephrine excretion, and systolic blood pressure. Angiotensin II infusion hypertrophied left ventricular (LV) without changing chamber dimensions while increased end-diastolic pressure. The LV pressure–volume relationship indicated that angiotensin II did not impact on the end-systolic elastance, whereas significantly increased end-diastolic elastance. Chronic intracerebroventricular infusion of AT1R blocker, losartan, attenuated these angiotensin II-induced changes. In conclusion, circulating angiotensin II in heart failure is capable of inducing sympathoexcitation via in part AT1R in the brain, subsequently leading to LV diastolic dysfunction.