Yamaleyeva Liliya M, Gallagher Patricia E, Vinsant Sharon, Chappell Mark C
Hypertension and Vascular Disease Center, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157-1095, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R819-26. doi: 10.1152/ajpregu.00389.2006. Epub 2006 Oct 5.
Estrogen depletion markedly exacerbates hypertension in female congenic mRen2. Lewis rats, a model of tissue renin overexpression. Because estrogen influences nitric oxide synthase (NOS) and NO may exert differential effects on blood pressure, the present study investigated the functional expression of NOS isoforms in the kidney of ovariectomized (OVX) mRen2. Lewis rats. OVX-mRen2. Lewis exhibited an increase in systolic blood pressure (SBP) of 171 +/- 5 vs. 141 +/- 7 mmHg (P < 0.01) for intact littermates. Renal cortical mRNA and protein levels for endothelial NOS (eNOS) were reduced 50-60% (P < 0.05) and negatively correlated with blood pressure. In contrast, cortical neuronal NOS (nNOS) mRNA and protein levels increased 100 to 300% (P < 0.05). In the OVX kidney, nNOS immunostaining was more evident in the macula densa, cortical tubules, and the medullary collecting ducts compared with the intact group. To determine whether the increase in renal nNOS expression constitutes a compensatory response to the reduction in renal eNOS, we treated both intact and OVX mRen2. Lewis rats with the selective nNOS inhibitor L-VNIO from 11 to 15 wk of age. The nNOS inhibitor reduced blood pressure in the OVX group (185 +/- 3 vs. 151 +/- 8 mmHg, P < 0.05), but pressure was not altered in the intact group (146 +/- 4 vs. 151 +/- 4 mmHg). In summary, exacerbation of blood pressure in the OVX mRen2. Lewis rats was associated with the discoordinate regulation of renal NOS isoforms. Estrogen sensitivity in this congenic strain may involve the influence of NO through the regulation of both eNOS and nNOS.
雌激素耗竭显著加剧了雌性同源mRen2. Lewis大鼠（一种组织肾素过表达模型）的高血压。由于雌激素影响一氧化氮合酶（NOS），且NO可能对血压产生不同影响，本研究调查了去卵巢（OVX）mRen2. Lewis大鼠肾脏中NOS亚型的功能表达。OVX - mRen2. Lewis大鼠的收缩压（SBP）相较于完整同窝大鼠升高至171±5 mmHg，而完整同窝大鼠为141±7 mmHg（P<0.01）。肾皮质中内皮型NOS（eNOS）的mRNA和蛋白水平降低了50 - 60%（P<0.05），且与血压呈负相关。相反，皮质神经元型NOS（nNOS）的mRNA和蛋白水平增加了100%至300%（P<0.05）。在OVX大鼠的肾脏中，与完整组相比，致密斑、皮质肾小管和髓质集合管中的nNOS免疫染色更明显。为了确定肾脏nNOS表达的增加是否构成对肾脏eNOS减少的代偿反应，我们在11至15周龄时用选择性nNOS抑制剂L - VNIO处理完整和OVX的mRen2. Lewis大鼠。nNOS抑制剂降低了OVX组的血压（185±3 mmHg对151±8 mmHg，P<0.05），但完整组血压未改变（146±4 mmHg对151±4 mmHg）。总之，OVX mRen2. Lewis大鼠血压的加剧与肾脏NOS亚型的失调调节有关。该同源品系中的雌激素敏感性可能涉及通过对eNOS和nNOS的调节而产生NO的影响。
