Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines
Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines
复制标题
长期将依那普利拉注入下丘脑室旁核可通过恢复神经递质和细胞因子来减轻血管紧张素 II 诱导的高血压和心脏肥大。
DOI：
10.1016/j.taap.2013.12.001
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发表时间：
2014-02-01
影响因子：
3.8
通讯作者：
Qin, Da-Nian
中科院分区：
文献类型：
--
作者：
Kang, Yu-Ming;Zhang, Dong-Mei;Qin, Da-Nian
脑内的肾素-血管紧张素系统（RAS）参与高血压的发病机制。我们假设抑制下丘脑室旁核（PVN）中的血管紧张素转换酶（ACE）通过恢复神经递质和细胞因子来减轻血管紧张素II（ANG II）诱导的高血压。大鼠接受皮下输注ANG II或生理盐水和双侧PVN输注ACE抑制剂依那普利拉（ENL，2.5 μ g/h）或载体4周。ANG II输注导致平均动脉压升高和心脏肥大，表现为全心重量/体重比、全心重量/胫骨长度比、左心室重量/胫骨长度比以及心脏心房利钠肽和β-肌球蛋白重链的mRNA表达增加。这些ANG II输注大鼠的PVN中谷氨酸、去甲肾上腺素、酪氨酸羟化酶、促炎细胞因子（PIC）和趋化因子单核细胞趋化蛋白-1水平较高，PVN中γ-氨基丁酸、白细胞介素（IL）-10和67-kDa谷氨酸脱羧酶（GAD 67）亚型水平较低，血浆PIC、去甲肾上腺素和醛固酮水平较高，血浆IL-10水平较低，和较高的肾交感神经活性。然而，PVN与ENL治疗减弱了这些变化。室旁核微量注射ANG II可引起室旁核IL-1 β和IL-6的升高，IL-10的降低，而预先用血管紧张素II 1型受体（AT 1-R）拮抗剂氯沙坦可减轻这些变化。这些发现表明，ANG II输注诱导兴奋性和抑制性神经递质之间的失衡以及PVN中促炎性和抗炎性细胞因子之间的失衡，并且PVN对RAS的抑制恢复PVN中的神经递质和细胞因子，从而减轻ANG II诱导的高血压和心脏肥大。(C)2013 Elsevier Inc. All rights reserved.
The renin-angiotensiri system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 mu g/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1 beta and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. (C) 2013 Elsevier Inc. All rights reserved.