Azilsartan attenuates cardiac damage caused by high salt intake through the downregulation of the cardiac (pro)renin receptor and its downstream signals in spontaneously hypertensive rats
Azilsartan attenuates cardiac damage caused by high salt intake through the downregulation of the cardiac (pro)renin receptor and its downstream signals in spontaneously hypertensive rats
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DOI：
10.1038/s41440-018-0099-0
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发表时间：
2018-11-01
影响因子：
5.4
通讯作者：
Minatoguchi, Shinya
中科院分区：
文献类型：
--
作者：
Komaki, Hisaaki;Iwasa, Masamitsu;Minatoguchi, Shinya
在高盐摄入的自发性高血压大鼠（SHR）中，我们检测了血管紧张素II AT 1受体的刺激是否增加心脏（原）肾素受体（（P）RR）及其下游信号的表达，以及阿齐沙坦对血管紧张素II AT 1受体的阻断是否降低心脏（P）RR及其信号的表达。大鼠从6 - 12周龄接受正常盐（0.9%）饲料、高盐（8.9%）饲料、正常盐饲料加1 mg/天阿齐沙坦和高盐饲料加1 mg/天阿齐沙坦。正常盐饲料的大鼠从6至12周龄通过渗透微泵给予100 ng/ kg/min的血管紧张素II。高盐饮食和血管紧张素II显著增加收缩压;过度表达心脏（P）RR，磷酸化（p）-ERK 1/2，p-p38 MAPK，p-HSP 27和TGF-B1;增加心脏间质和血管周围纤维化，心肌细胞大小，室间隔（IVS）厚度和左心室（LV）舒张末期尺寸;降低LV缩短分数。阿齐沙坦可降低收缩压，降低心脏（P）RR、p-ERK 1/2、p-p38 MAPK、p-HSP 27和TGF-B1的表达，降低心脏间质和血管周围纤维化，减小心肌细胞大小，降低左室舒张期内径，改善左室短轴缩短率。总之，阿齐沙坦通过下调心脏（原）肾素受体及其下游信号减轻高盐摄入引起的心脏损伤。
We examined whether the stimulation of the angiotensin II AT1 receptor increases the expression of the cardiac (pro)renin receptor ((P)RR) and its downstream signals and whether the blockade of the angiotensin II AT1 receptor by azilsartan decreases the expression of the cardiac (P)RR and its signaling in spontaneously hypertensive rats (SHRs) with a high-salt intake. Rats received normal-salt (0.9%) chow, high-salt (8.9%) chow, normal-salt chow with 1 mg/day of azilsartan, and high-salt chow with 1 mg/day of azilsartan from 6 to 12 weeks of age. Rats with normal-salt chow were administered 100 ng/ kg/min of angiotensin II by osmotic minipump from 6 to 12 weeks of age. A high-salt diet and angiotensin II significantly increased the systolic blood pressure; overexpressed cardiac (P)RR, phosphorylated (p)-ERK1/2, p-p38MAPK, p-HSP27, and TGF-B1; enhanced cardiac interstitial and perivascular fibrosis, cardiomyocyte size, interventricular septum (IVS) thickness, and left ventricular (LV) end-diastolic dimension; and decreased LV fractional shortening. Azilsartan decreased systolic blood pressure, cardiac expressions of (P)RR, p-ERK1/2, p-p38MAPK, p-HSP27, and TGF-B1, cardiac interstitial and perivascular fibrosis, cardiomyocyte size, and LV diastolic dimension, and improved LV fractional shortening. In conclusion, azilsartan attenuates cardiac damage caused by high salt intake through the downregulation of the cardiac (pro) renin receptor and its downstream signals in SHRs.