Connexin43-dependent mechanism modulates renin secretion and hypertension
Connexin43-dependent mechanism modulates renin secretion and hypertension
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DOI：
10.1172/jci23327
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发表时间：
2006-02-01
影响因子：
15.9
通讯作者：
Meda, P
中科院分区：
文献类型：
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作者：
Haefliger, JA;Krattinger, N;Meda, P
为了研究Cx43在高血压中的功能，我们研究了小鼠品系Cx43 KI 32（KI 32），其中Cx32的编码区取代Cx43的编码区。在KI32纯合子小鼠的肾脏中，Cx32在皮质和髓质小管以及一些肾小球外和肾小球内血管中表达，即，在WT小鼠中发现Cx32和Cx43的位点。在这种条件下，与WT和杂合KI 32同窝仔的肾脏中观察到的相比，肾素表达大大降低。在暴露于高盐饮食后，所有小鼠的血压都保持正常。然而，尽管WT和杂合子KI 32小鼠肾脏中的肾素水平显著降低，达到与纯合子同窝小鼠中观察到的水平相当的水平，但在后者动物中未受到进一步影响。肾动脉夹闭后4周（2肾1夹[2K1C]模型），2K1C WT和杂合子小鼠显示血压和循环肾素水平升高，而2K1C纯合子同窝小鼠血压保持正常，血浆肾素活性不变。高血压小鼠也发生了心脏肥大，但血压正常的小鼠没有。这些数据表明，Cx32取代Cx43与降低的肾素表达和分泌有关，从而防止了在2K1C模型中正常诱导的肾素依赖性高血压。
To investigate the function of Cx43 during hypertension, we studied the mouse line Cx43KI32 (KI32), in which the coding region of Cx32 replaces that of Cx43. Within the kidneys of homozygous KI32 mice, Cx32 was expressed in cortical and medullary tubules, as well as in some extra- and intraglomerular vessels, i.e., at sites where Cx32 and Cx43 are found in WT mice. Under such conditions, renin expression was much reduced compared with that observed in the kidneys of WT and heterozygous KI32 littermates. After exposure to a high-salt diet, all mice retained a normal blood pressure. However, whereas the levels of renin were significantly reduced in the kidneys of WT and heterozygous KI32 mice, reaching levels comparable to those observed in homozygous littermates, they were not further affected in the latter animals. Four weeks after the clipping of a renal artery (the 2-kidney, 1-clip [2K1C] model), 2K1C WT and heterozygous mice showed an increase in blood pressure and in the circulating levels of renin, whereas 2K1C homozygous littermates remained normotensive and showed unchanged plasma renin activity. Hypertensive, but not normotensive, mice also developed cardiac hypertrophy. The data indicate that replacement of Cx43 by Cx32 is associated with decreased expression and secretion of renin, thus preventing the renin-dependent hypertension that is normally induced in the 2K1C model.