Effects of central hypocretin-1 administration on hemodynamic responses in young-adult and middle-aged rats
Effects of central hypocretin-1 administration on hemodynamic responses in young-adult and middle-aged rats
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DOI：
10.1016/s0006-8993(03)03002-6
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发表时间：
2003-08-15
期刊：
影响因子：
2.9
通讯作者：
Matsuki, A
中科院分区：
文献类型：
--
作者：
Hirota, K;Kushikata, T;Matsuki, A
中年高血压的患病率与自主神经调节受损相关，并且随着年龄的增长，去甲肾上腺素能神经元下降，这种下降可能有助于这种损害。中枢下丘脑泌素激活的去甲肾上腺素能神经元参与交感神经调节。在本研究中，我们比较了侧脑室（i. c. v.）下丘脑泌素-1（5 nmol）在成年大鼠（12-14周）和中年大鼠（12-14个月）之间的变化。在戊巴比妥麻醉下测定动脉血压、心率和血浆儿茶酚胺。此外，我们比较了下丘脑泌素-1和K+-诱发的去甲肾上腺素释放的大脑皮层切片制备的成年和中年大鼠。我们还研究了新的下丘脑泌素受体-1拮抗剂（SB-334867）是否可以在体内和体外逆转这些下丘脑泌素-1的作用。下丘脑泌素-1在成年大鼠中显著增加血压约7%，心率9%，血浆去甲肾上腺素浓度100%。在中年大鼠中，这些参数没有变化。两组血浆肾上腺素均未增加。平均动脉压的变化与血浆去甲肾上腺素之间存在显著相关性。同样，下丘脑泌素-1诱发的去甲肾上腺素释放从成年大鼠的大脑皮层切片制备的显着高于中年大鼠，而K+诱发的释放没有组间差异。SB-334867显著减弱下丘脑泌素-1升高的血压以及体内和体外去甲肾上腺素释放。目前的数据表明，下丘脑泌素能神经元可能有助于调节中枢，但不是肾上腺交感神经活性。此外，交感神经调节下丘脑泌素能神经元可能会消失，在中年大鼠。(C)2003 Elsevier B. V.保留所有权利。
The prevalence of hypertension in middle age correlates with impaired autonomic regulation and as norepinephrinergic neurons decline with increasing age, and this reduction may contribute to this impairment. Central hypocretin-activated norepinephrinergic neurons contribute to sympathetic regulation. In the present study we compared sympathoadrenal effects of intracerebroventricular (i.c.v.) hypocretin-1(5 nmol) between young-adult (12-14 weeks) and middle-aged (12-14 months) rats. Arterial blood pressure, heart rate and plasma catecholamines were assessed under pentobarbital anesthesia. In addition, we compared hypocretin-1 and K+-evoked norepinephrine release from the cerebrocortical slices prepared from young-adult and middle-aged rats. We also examined whether the novel hypocretin receptor-1 antagonist (SB-334867) could reverse these hypocretin-1 effects both in vivo and in vitro. I.c.v. hypocretin-1 significantly increased blood pressure by some 7%, heart rate by 9% and plasma norepinephrine concentrations by 100% in young-adult rats. In middle-aged rats these parameters did not change. Plasma epinephrine did not increase in either group. There was a significant correlation between changes in mean arterial pressure and plasma norepinephrine. Similarly, hypocretin-1 evoked norepinephrine release from cerebrocortical slices prepared from young-adult rats was significantly higher than that of middle-aged rats whilst K+-evoked release did not differ between the groups. SB-334867 significantly attenuated hypocretin-1-increased blood pressure and both in vivo and in vitro norepinephrine release. The present data suggest that hypocretinergic neurons may contribute to the regulation of central but not adrenal sympathetic activity. Moreover, sympathetic regulation by hypocretinergic neurones may disappear in middle-age in rats. (C) 2003 Elsevier B.V. All rights reserved.