Neuronal nitric oxide synthase within paraventricular nucleus: blood pressure and baroreflex in two-kidney, one-clip hypertensive rats.
Neuronal nitric oxide synthase within paraventricular nucleus: blood pressure and baroreflex in two-kidney, one-clip hypertensive rats.
复制标题
DOI：
10.1113/expphysiol.2009.051789
复制
发表时间：
2010-08
影响因子：
2.7
通讯作者：
Augustyniak RA
中科院分区：
文献类型：
--
作者：
Rossi NF;Maliszewska-Scislo M;Chen H;Black SM;Sharma S;Ravikov R;Augustyniak RA
肾素血管紧张素系统在两肾一夹压高血压的早期被激活。室旁核（PVN）整合调节交感神经流出的输入。 PVN 通过来自室周器官的投射和通过孤束核传输的肾传入神经接收来自血浆血管紧张素 II 的输入。 PVN 内的一氧化氮可能发挥交感神经抑制作用。这些研究测试了通过将神经元一氧化氮合酶 (nNOS) 的显性失活 (DN) 结构引入 PVN 来减少内源性一氧化氮是否会长期增加高血压和/或调节压力反射功能。六周大的雄性斯普拉格道利大鼠接受了假肾动脉或右肾动脉夹闭和无线电遥测发射器的放置。一周后，PVN双侧注射250 nl含有250 ng/μl RSV β-半乳糖苷酶（β-gal）的人工脑脊液； CMV 野生型（WT nNOS）；或RSV血红素结构域或RSV hemeRedF (DN nNOS)。监测血流动力学五周。然后放置左肾神经电极，两天后在清醒状态下对大鼠进行压力反射测试。 PVN 注射后 15 天后，DN nNOS 2K-1C 组中 MAP 的升高显着增强。到第 35 天，2K-1C 组的 MAP 为 152±6.3 (β-gal)、155.1±6.6 (WT nNOS) 和 179±5.4 mmHg（DN nNOS，与所有其他组相比 P<0.01）。假剪毛的大鼠血压保持正常。随着时间的推移，所有组均表现出进行性心动过缓，而 DN nNOS 2K-1C 组的情况有所减弱。在所有 2K-1C 组大鼠中，压力反射曲线转向更高的压力，并且 HR 的压力反射敏感性同样降低。 RSNA 的压力反射反应得以保留。 DN nNOS 大鼠的 PVN 组织中 nNOS 的二聚化和 NOx 的生成减少。这些发现表明，PVN 内生成一氧化氮所需的 nNOS 二聚化的慢性干扰通过调节伴随肾血管性高血压的交感兴奋而增强血压升高。
The renin angiotensin system is activated in the early phase of two-kidney one-clip hypertension. The paraventricular nucleus (PVN) integrates inputs regulating sympathetic outflow. The PVN receives inputs from plasma angiotensin II via projections from circumventricular organs and from renal afferent nerves transmitted via the nucleus tractus solitarius. Nitric oxide within the PVN may exert a sympathoinhibitory effect. These studies tested whether decreasing endogenous nitric oxide by introducing dominant negative (DN) constructs for neuronal nitric oxide synthase (nNOS) into PVN chronically augments hypertension and/or modulates baroreflex function. Male six-week old Sprague Dawley rats underwent sham or right renal artery clipping and placement of radiotelemetry transmitters. One week later, the PVN was injected bilaterally with 250 nl artificial CSF containing 250 ng/μl of RSV β-galactosidase (β-gal); CMV wild type (WT nNOS); or RSV heme domain or RSV hemeRedF (DN nNOS). Hemodynamics were monitored for five weeks. Then left renal nerve electrodes were placed, and two days later the rats underwent baroreflex testing in the conscious state. The rise in MAP was significantly potentiated in the DN nNOS 2K-1C group beyond 15 days after PVN injection. By day 35, MAP in the 2K-1C groups was 152±6.3 (β-gal), 155.1±6.6 (WT nNOS) and 179±5.4 mmHg (DN nNOS, P<0.01 vs all other groups). Sham-clipped rats remained normotensive. All groups displayed progressive bradycardia over time that was attenuated in the DN nNOS 2K-1C group. Baroreflex curves shifted to higher pressures and baroreflex sensitivity of HR was diminished similarly in all groups of 2K-1C rats. The baroreflex response of RSNA was preserved. PVN tissue from DN nNOS rats had decreased dimerization of nNOS and generation of NOx. These findings indicate that chronic interference of nNOS dimerization required for generation of nitric oxide within the PVN potentiates the increase of blood pressure by modulating the sympathoexcitation that accompanies renovascular hypertension.
登录
查看更多内容
影响因子：
2.1
作者：
Gava, Agata L.;Peotta, Veronica A.;Meyrelles, Silvana S.
通讯作者：
Meyrelles, Silvana S.
影响因子：
8.3
作者：
KOPP, UC;BUCKLEYBLEILER, RL
通讯作者：
BUCKLEYBLEILER, RL
影响因子：
2.9
作者：
DiCarlo, SE;Zheng, H;Patel, KP
通讯作者：
Patel, KP
影响因子：
2.9
作者：
Giles, ME;Sly, DJ;Oldfield, BJ
通讯作者：
Oldfield, BJ
DOI：
10.1152/ajpregu.00157.2008
发表时间：
2008-09-01
影响因子：
2.8
作者：
Maliszewska-Scislo, Maria;Chen, Haiping;Rossi, Noreen F.
通讯作者：
Rossi, Noreen F.