Zhao X, White R, Van Huysse J, Leenen F H
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
J Hypertens. 2000 Sep;18(9):1319-26. doi: 10.1097/00004872-200018090-00018.
On high salt intake, Dahl salt-sensitive rats develop cardiac hypertrophy disproportionate to the degree of hypertension. In the present studies, we assessed whether the cardiac hypertrophy induced by high salt depends on the development of hypertension per se, and leads to over-activity of the cardiac renin-angiotensin system (RAS).
Cardiac angiotensin converting enzyme (ACE) mRNA and activity, cardiac and plasma angiotensin I and II (AngI, II), as well as plasma renin activity (PRA) were assessed in Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats on high (1370 micromol/g food) or regular salt (120 micromol/g food) diet for 2-5 weeks. Cardiac ACE and hypertrophic response in Dahl S on high salt were also assessed after central blockade of sympathetic hyperactivity and hypertension.
In Dahl S rats, ACE mRNA and activity of the left ventricle (LV) increased markedly after 4-5 weeks of high salt diet compared with Dahl S on the control diet and Dahl R on either diet Chronic intra-cerebroventricular treatment with Fab fragments blocking brain 'ouabain' prevented the hypertension by high salt in Dahl S rats but did not affect the salt-induced increases in LV weight or in LV ACE mRNA and activity. On regular salt diet, Dahl S rats demonstrated significantly lower cardiac AngI and AngII than Dahl R rats. However, high salt intake did not cause significant changes in cardiac AngI and II in either strain. On regular salt diet, PRA, plasma AngI and II were all significantly lower in Dahl S versus R. In Dahl S rats, high salt did not cause further decreases of the already low PRA or plasma AngI and II.
These data indicate a low activity of both circulatory and cardiac RAS in Dahl S versus R rats. The marked cardiac hypertrophy and increase in cardiac ACE mRNA and activity induced by high salt in Dahl S do not depend on the increase in blood pressure. High salt intake did not increase cardiac AngII in Dahl S, suggesting that the increase in ACE mRNA and activity may be relevant for non-angiotensinergic mechanisms involved in cardiac hypertrophy.
在高盐摄入情况下，Dahl盐敏感大鼠会出现与高血压程度不相称的心脏肥大。在本研究中，我们评估了高盐诱导的心脏肥大是否依赖于高血压本身的发展，以及是否会导致心脏肾素 - 血管紧张素系统（RAS）过度激活。
对Dahl盐敏感（Dahl S）和盐抵抗（Dahl R）大鼠给予高盐（1370微摩尔/克食物）或常规盐（120微摩尔/克食物）饮食2 - 5周，评估其心脏血管紧张素转换酶（ACE）mRNA和活性、心脏及血浆血管紧张素I和II（AngI、II）以及血浆肾素活性（PRA）。在交感神经过度活跃和高血压的中枢阻断后，还评估了高盐饮食下Dahl S大鼠的心脏ACE和肥大反应。
与对照饮食的Dahl S大鼠和两种饮食下的Dahl R大鼠相比，高盐饮食4 - 5周后，Dahl S大鼠左心室（LV）的ACE mRNA和活性显著增加。用Fab片段慢性脑室内治疗阻断脑“哇巴因”可预防Dahl S大鼠因高盐引起的高血压，但不影响盐诱导的LV重量增加或LV ACE mRNA和活性增加。在常规盐饮食下，Dahl S大鼠的心脏AngI和AngII明显低于Dahl R大鼠。然而，高盐摄入在两种品系中均未引起心脏AngI和II的显著变化。在常规盐饮食下，Dahl S大鼠的PRA、血浆AngI和II均显著低于Dahl R大鼠。在Dahl S大鼠中，高盐并未导致本已较低的PRA或血浆AngI和II进一步降低。
这些数据表明，与Dahl R大鼠相比，Dahl S大鼠的循环和心脏RAS活性较低。高盐在Dahl S大鼠中诱导的明显心脏肥大以及心脏ACE mRNA和活性增加并不依赖于血压升高。高盐摄入并未增加Dahl S大鼠的心脏AngII，提示ACE mRNA和活性增加可能与参与心脏肥大的非血管紧张素能机制有关。
