Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A
Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A
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DOI：
10.1073/pnas.94.26.14730
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发表时间：
1997-12-23
影响因子：
11.1
通讯作者：
Maeda, N
中科院分区：
文献类型：
--
作者：
Oliver, PM;Fox, JE;Maeda, N
在心脏中产生的利钠肽与利钠肽受体A （NPRA）结合，引起血管舒张和利钠，在血压调节中起重要作用。我们在这里报道，缺乏功能性Npr1基因编码NPRA的小鼠血压升高，心脏表现出明显的肥大和间质纤维化，与人类高血压心脏病相似。超声心动图评估显示，小鼠处于全体性高血压代偿状态，心脏肥厚和扩张明显，但心室功能没有下降。然而，形态学证据表明，在一些充血性心力衰竭和其他主动脉夹层的动物中，所有15只缺乏Npr1的雄性小鼠在6个月前都发生了猝死，在我们的研究中，16只雌性小鼠中有一只发生了猝死。因此，完全缺乏NPRA会导致小鼠高血压，并导致心脏肥厚，特别是在雄性中，致命的血管事件与未经治疗的人类高血压患者相似。
Natriuretic peptides, produced in the heart, bind to the natriuretic peptide receptor A (NPRA) and cause vasodilation and natriuresis important in the regulation of blood pressure, We here report that mice lacking a functional Npr1 gene coding for NPRA have elevated blood pressures and hearts exhibiting marked hypertrophy with interstitial fibrosis resembling that seen in human hypertensive heart disease, Echocardiographic evaluation of the mice demonstrated a compensated state of systemic hypertension in which cardiac hypertrophy and dilatation are evident but with no reduction in ventricular performance, Nevertheless, sudden death, with morphologic evidence indicative in some animals of congestive heart failure and in others of aortic dissection, occurred in all 15 male mice lacking Npr1 before 6 months of age, and in one of 16 females in our study, Thus complete absence of NPRA causes hypertension in mice and leads to cardiac hypertrophy and, particularly in males, lethal vascular events similar to those seen in untreated human hypertensive patients.