AT1 and glutamatergic receptors in paraventricular nucleus support blood pressure during water deprivation
AT1 and glutamatergic receptors in paraventricular nucleus support blood pressure during water deprivation
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DOI：
10.1152/ajpregu.00623.2006
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发表时间：
2007-04-01
影响因子：
2.8
通讯作者：
Brooks, Virginia L.
中科院分区：
文献类型：
--
作者：
Freeman, Korrina L.;Brooks, Virginia L.
缺水会激活室旁核（PVN）的交感兴奋神经元；然而，介导这种激活的神经递质尚不清楚。为了检验 ANG II 和谷氨酸参与的假设，在乌拉烷麻醉的缺水和充足水的雄性大鼠中测定了双侧 PVN 显微注射 ANG II 1 型受体 (AT1R) 拮抗剂坎地沙坦和缬沙坦或离子型谷氨酸受体拮抗剂犬尿酸盐对血压 (BP) 的影响。由于 PVN 可能通过延髓头端腹外侧 (RVLM) 激活交感神经元，并且由于 PVN 去抑制部分通过增加 RVLM 中 AT1R 的驱动而增加交感神经活动，因此坎地沙坦也被双侧显微注射到 RVLM 中。双侧显微注射蝇蕈醇（一种 GABA(A) 激动剂）完全阻断 PVN，在缺水 (-29 +/- 8 mmHg) 大鼠中比在充足水 (-7 +/- 2 mmHg) 大鼠中更能降低血压 (P < 0.05)，证实在缺水期间 PVN 是维持血压所必需的。 PVN 坎地沙坦使血压缓慢降低 7 +/- 1 mmHg (P < 0.05)。然而，在充足水的大鼠中，坎地沙坦不会改变血压（1 +/- 1 mmHg）。缬沙坦还使缺水大鼠的动脉压缓慢下降（-6 +/- 1 mmHg；P < 0.05），但在充足水（-1 +/- 1 mmHg）大鼠中则不然。在缺水的大鼠中，PVN 犬尿酸盐迅速降低血压 (-19 +/- 3 mmHg)，且反应比充足水的大鼠 (-4 +/- 1 mmHg) 更大 (P < 0.05)。最后，与PVN一样，RVLM中的坎地沙坦可缓慢降低缺水大鼠的血压（-8 +/- 1 mmHg；P < 0.05），但在充足水（-3 +/- 1 mmHg）大鼠中则不然。这些数据表明，PVN 中 AT(1) 和谷氨酸受体以及 RVLM 中 AT1R 的激活有助于缺水期间血压的维持。
Water deprivation activates sympathoexcitatory neurons in the paraventricular nucleus (PVN); however, the neurotransmitters that mediate this activation are unknown. To test the hypothesis that ANG II and glutamate are involved, effects on blood pressure (BP) of bilateral PVN microinjections of ANG II type 1 receptor (AT1R) antagonists, candesartan and valsartan, or the ionotropic glutamate receptor antagonist, kynurenate, were determined in urethane-anesthetized water-deprived and water-replete male rats. Because PVN may activate sympathetic neurons via the rostral ventrolateral medulla (RVLM) and because PVN disinhibition increases sympathetic activity in part via increased drive of AT1R in the RVLM, candesartan was also bilaterally microinjected into the RVLM. Total blockade of the PVN with bilateral microinjections of muscimol, a GABA(A) agonist, decreased BP more (P < 0.05) in water-deprived (-29 +/- 8 mmHg) than in water-replete (-7 +/- 2 mmHg) rats, verifying that the PVN is required for BP maintenance during water deprivation. PVN candesartan slowly lowered BP by 7 +/- 1 mmHg (P < 0.05). In water-replete rats, however, candesartan did not alter BP (1 +/- 1 mmHg). Valsartan also produced a slowly developing decrease in arterial pressure (-6 +/- 1 mmHg; P < 0.05) in water-deprived but not in water-replete (-1 +/- 1 mmHg) rats. In water-deprived rats, PVN kynurenate rapidly decreased BP (-19 +/- 3 mmHg), and the response was greater (P < 0.05) than in water-replete rats (-4 +/- 1 mmHg). Finally, as in PVN, candesartan in RVLM slowly decreased BP in water-deprived (-8 +/- 1 mmHg; P < 0.05) but not in water-replete (-3 +/- 1 mmHg) rats. These data suggest that activation of AT(1) and glutamate receptors in PVN, as well as of AT1R in RVLM, contributes to BP maintenance during water deprivation.