Veerasingham S J, Vahid-Ansari F, Leenen F H
Hypertension Unit H360, University of Ottawa Heart Institute and Departments of Cellular and Molecular Medicine, and Medicine, 40 Ruskin Street, University of Ottawa, Ontario K1Y 4W7, Ottawa, Canada.
Brain Res. 2000 Sep 8;876(1-2):17-21. doi: 10.1016/s0006-8993(00)02591-9.
In normotensive Wistar rats, systemic administration of exogenous ouabain for 10 days or more induces hypertension, presumably through central mechanisms. To identify which neuronal populations may be involved, we assessed Fos-like immunoreactivity (FLI) using an antibody that recognizes the protein products of the fos family comprising Fos, Fos B, Fra 1 and Fra 2, thus enabling detection of chronic neuronal activation. Young Wistar rats received s.c. infusions of either ouabain (50 microg/day) or saline for 7 or 14 days. At the end of the experimental period, mean arterial pressure (MAP) was assessed. In a separate set of rats FLI was detected immunohistochemically and quantified in cardiovascular and osmo-regulating centers. Resting MAP in ouabain-treated rats was significantly higher than in control rats at 14 but not at 7 days (125+/-4 vs. 101+/-6, P<0.05 and 102+/-4 vs. 98+/-6 (not significant), respectively). Within the supraoptic nucleus, ouabain induced significant increases in FLI compared with control rats at 14 days (9+/-2 vs. 2+/-2, P<0.05) but not at 7 days. Within the locus ceruleus, FLI was only detectable in rats that received ouabain infusions for 14 days but not in other groups of rats. Ouabain treatment did not induce significant changes in FLI within other areas. These results demonstrate that chronic s.c. ouabain infusion only increases neuronal FLI in the supraoptic nucleus and locus ceruleus where increases in FLI parallel the increase in blood pressure.
在血压正常的Wistar大鼠中,全身给予外源性哇巴因10天或更长时间会诱发高血压,推测是通过中枢机制。为了确定哪些神经元群体可能参与其中,我们使用一种能识别fos家族蛋白质产物(包括Fos、Fos B、Fra 1和Fra 2)的抗体评估Fos样免疫反应性(FLI),从而能够检测慢性神经元激活。年轻的Wistar大鼠皮下注射哇巴因(50微克/天)或生理盐水,持续7天或14天。在实验期结束时,评估平均动脉压(MAP)。在另一组大鼠中,通过免疫组织化学检测FLI,并在心血管和渗透压调节中枢进行定量分析。哇巴因处理的大鼠在14天时静息MAP显著高于对照组大鼠,但在7天时无显著差异(分别为125±4与101±6,P<0.05;102±4与98±6(无显著差异))。在视上核内,与对照组大鼠相比,哇巴因在14天时诱导FLI显著增加(9±2与2±2,P<0.05),但在7天时无此现象。在蓝斑核内,仅在接受哇巴因注射14天的大鼠中可检测到FLI,其他组大鼠中未检测到。哇巴因处理在其他区域未诱导FLI发生显著变化。这些结果表明,慢性皮下注射哇巴因仅增加视上核和蓝斑核中的神经元FLI,其中FLI的增加与血压升高平行。