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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Simvastatin reverses cardiac hypertrophy caused by disruption of the bradykinin 2 receptor.
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Simvastatin reverses cardiac hypertrophy caused by disruption of the bradykinin 2 receptor.

机译：辛伐他汀逆转由缓激肽2受体破坏引起的心脏肥大。

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摘要

Bradykinin 2 receptor (B2R) deficiency predisposes to cardiac hypertrophy and hypertension. The pathways mediating these effects are not known. Two-month-old B2R knockout (KO) and wild-type (WT) mice were assigned to 4 treatment groups (n = 12-14/group): control (vehicle); nitro-L-arginine methyl ester (L-NAME) an NO synthase inhibitor; simvastatin (SIM), an NO synthase activator; and SIM+L-NAME. Serial echocardiography was performed and blood pressure (BP) at 6 weeks was recorded using a micromanometer. Myocardial eNOS and mitogen-activated protein kinase (MAPK, including ERK, p38, and JNK) protein expression were measured. Results showed that (i) B2RKO mice had significantly lower ejection fraction than did WT mice (61% +/- 1% vs. 73% +/- 1%), lower myocardial eNOS and phospho-eNOS, normal systolic BP, and higher LV mass, phospho-p38, and JNK; (ii) L-NAME increased systolic BP in KO mice (117 +/- 19 mm Hg) but not in WT mice and exacerbated LV hypertrophy and dysfunction; and (iii) in KO mice, SIM decreased hypertrophy, p38, and JNK, improved function, increased capillary eNOS and phospho-eNOS, and prevented L-NAME-induced LV hypertrophy without lowering BP. We conclude that disruption of the B2R causes maladaptive cardiac hypertrophy with myocardial eNOS downregulation and MAPK upregulation. SIM reverses these abnormalities and prevents the development of primary cardiac hypertrophy as well as hypertrophy secondary to L-NAME-induced hypertension.
机译：缓激肽2受体（B2R）缺乏易患心脏肥大和高血压。介导这些作用的途径尚不清楚。将两个月大的B2R基因敲除（KO）和野生型（WT）小鼠分为4个治疗组（n = 12-14 /组）：对照组（媒介物）;硝基-L-精氨酸甲酯（L-NAME），NO合酶抑制剂;辛伐他汀（SIM），NO合酶激活剂;和SIM + L-NAME。进行连续超声心动图检查，并使用微量压力计记录6周时的血压（BP）。测量了心肌eNOS和丝裂原活化蛋白激酶（MAPK，包括ERK，p38和JNK）的蛋白表达。结果显示（i）B2RKO小鼠的射血分数显着低于WT小鼠（61％+/- 1％vs. 73％+/- 1％），较低的心肌eNOS和磷酸化eNOS，正常的收缩压以及更高的LV质量，phospho-p38和JNK; （ii）L-NAME增加了KO小鼠（117 +/- 19 mm Hg）的收缩压，但不降低WT小鼠的收缩压，加剧了LV肥大和功能障碍; （iii）在KO小鼠中，SIM减少了肥大，p38和JNK，改善了功能，增加了毛细血管eNOS和磷酸化eNOS，并在不降低BP的情况下预防了L-NAME诱导的LV肥大。我们得出的结论是，B2R的破坏会导致心肌eNOS下调和MAPK上调而导致适应不良的心肌肥大。 SIM可逆转这些异常现象，并防止原发性心脏肥大以及继L-NAME诱发的高血压之后的肥大。

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