Harrison-Bernard Lisa M, Schulman Ivonne Hernandez, Raij Leopoldo
Department of Physiology, SL39 Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112-2699, USA.
Hypertension. 2003 Dec;42(6):1157-63. doi: 10.1161/01.HYP.0000102180.13341.50. Epub 2003 Nov 10.
The functional balance between angiotensin II (Ang II) and nitric oxide (NO) plays a key role in modulating salt sensitivity. Estrogen has been shown to downregulate angiotensin type 1 (AT1) receptor expression and to increase the bioavailability of endothelium-derived NO, which decreases AT1 receptor expression. The present study tests the hypothesis that in the presence of genetic salt sensitivity, deficiency of endogenous estrogens after ovariectomy (OVX) fosters an upregulation of Ang II. Female Dahl salt-resistant (DR), Dahl salt-sensitive (DS), Wistar-Kyoto (WKY), and spontaneously hypertensive (SHR) rats underwent bilateral OVX or sham surgery (SHX) and were fed a normal salt diet (0.5% NaCl) for 14 weeks. Systolic blood pressures were measured every 2 weeks and were not significantly different between OVX and SHX for DR, WKY, and SHR groups. However, at the end of 14 weeks of normal salt diet, hypertension developed in DS OVX but not SHX rats (160+/-3 versus 136+/-3 mm Hg; P<0.05). Hypertension also developed in DS OVX rats pair-fed a normal salt diet (166+/-7 mm Hg). Development of hypertension in DS OVX rats was prevented by estrogen replacement (132+/-3 mm Hg), AT1 receptor blockade (119+/-3 mm Hg), or feeding a very low salt diet (0.1% NaCl; 129+/-4 mm Hg). Renal AT1 receptor protein expression was significantly elevated 2-fold in DS OVX relative to SHX rats and was prevented by estrogen replacement. These data strongly suggest that after OVX in salt-sensitive rats there is a lower threshold for the hypertensinogenic effect of salt that is linked to an activation of Ang II.
血管紧张素II（Ang II）与一氧化氮（NO）之间的功能平衡在调节盐敏感性方面起着关键作用。雌激素已被证明可下调血管紧张素1型（AT1）受体的表达，并增加内皮源性NO的生物利用度，从而降低AT1受体的表达。本研究检验了这样一个假设：在存在遗传性盐敏感性的情况下，卵巢切除术后（OVX）内源性雌激素的缺乏会促进Ang II的上调。雌性 Dahl 盐抵抗（DR）大鼠、Dahl 盐敏感（DS）大鼠、Wistar-Kyoto（WKY）大鼠和自发性高血压（SHR）大鼠接受双侧卵巢切除术或假手术（SHX），并给予正常盐饮食（0.5% NaCl）14周。每2周测量一次收缩压，DR、WKY和SHR组的OVX和SHX大鼠之间收缩压无显著差异。然而，在正常盐饮食14周结束时，DS OVX大鼠而非SHX大鼠出现了高血压（160±3 与 136±3 mmHg；P<0.05）。配对给予正常盐饮食的DS OVX大鼠也出现了高血压（166±7 mmHg）。雌激素替代（132±3 mmHg）、AT1受体阻断（119±3 mmHg）或给予极低盐饮食（0.1% NaCl；129±4 mmHg）可预防DS OVX大鼠高血压的发生。与SHX大鼠相比，DS OVX大鼠肾AT1受体蛋白表达显著升高2倍，而雌激素替代可预防这种升高。这些数据有力地表明，盐敏感大鼠卵巢切除术后，盐的致高血压作用阈值降低，这与Ang II的激活有关。
