Ni Z, Vaziri N D
Department of Medicine, University of California, Irvine, USA.
Am J Hypertens. 2001 Feb;14(2):155-63. doi: 10.1016/s0895-7061(00)01234-6.
Elevation of arterial blood pressure (BP) with high salt intake in Dahl salt-sensitive rats is associated and perhaps, in part, due to downregulation of renal and vascular production of nitric oxide (NO) and nitric oxide synthase (NOS) expressions. Several recent studies have revealed a significant increase in BP in Sprague-Dawley rats on high salt intake. Given the apparent salt sensitivity of Sprague-Dawley rats, we hypothesized that chronic high salt intake may affect NO system in these rats in a manner resembling that reported in salt-sensitive (not salt-resistant) Dahl rats. The effects of a high salt diet (chow containing 8% NaCl) of 48-h or 3-week duration was studied on immunodetectable endothelial (eNOS), inducible (iNOS), and neuronal (nNOS) NOS expressions of relevant organs in male Sprague-Dawley rats. The results were compared with those obtained in the control animals fed a regular no-added salt diet (0.2% NaCl). Consumption of a high salt diet for 3 weeks induced hypertension (HTN) (158 +/- 6 v 115 +/- 5 mm Hg, P < .01) and widespread downregulation of iNOS expression in renal cortex, renal medulla, aorta, and heart. Similarly, chronic salt loading resulted in marked downregulation of eNOS expression in renal cortex and aorta and lowered expressions of nNOS in the brain, renal cortex, and renal medulla. In comparison, short-term salt loading resulted in significant reduction of iNOS in the renal cortex and aorta and of eNOS in the aorta together with significant elevation of nNOS expression in renal medulla and brain. Thus, chronic consumption of a high salt diet resulted in moderate HTN in normotensive Sprague-Dawley rats. This was accompanied by widespread downregulation of various NOS isotypes that undoubtedly contributed to the development and maintenance of HTN in this model.
在 Dahl 盐敏感大鼠中，高盐摄入导致动脉血压（BP）升高，这可能部分归因于肾脏和血管中一氧化氮（NO）生成及一氧化氮合酶（NOS）表达的下调。最近的几项研究表明，高盐摄入的 Sprague-Dawley 大鼠血压显著升高。鉴于 Sprague-Dawley 大鼠明显的盐敏感性，我们推测慢性高盐摄入可能以类似于盐敏感（而非盐抵抗）Dahl 大鼠的方式影响这些大鼠的 NO 系统。研究了持续 48 小时或 3 周的高盐饮食（含 8% NaCl 的饲料）对雄性 Sprague-Dawley 大鼠相关器官中可免疫检测到的内皮型（eNOS）、诱导型（iNOS）和神经元型（nNOS）NOS 表达的影响。将结果与喂食常规无添加盐饮食（0.2% NaCl）的对照动物所得结果进行比较。食用 3 周高盐饮食会诱发高血压（HTN）（158±6 对 115± mmHg，P<.01），并导致肾皮质、肾髓质、主动脉和心脏中 iNOS 表达广泛下调。同样，慢性盐负荷导致肾皮质和主动脉中 eNOS 表达显著下调，大脑、肾皮质和肾髓质中 nNOS 表达降低。相比之下，短期盐负荷导致肾皮质和主动脉中 iNOS 显著减少，主动脉中 eNOS 减少，同时肾髓质和大脑中 nNOS 表达显著升高。因此，正常血压的 Sprague-Dawley 大鼠长期食用高盐饮食会导致中度 HTN。这伴随着各种 NOS 同工型的广泛下调，无疑促成了该模型中 HTN 的发生和维持。
