Cardiovascular actions of orexin-A in the rat subfornical organ.
Cardiovascular actions of orexin-A in the rat subfornical organ.
复制标题
食欲素-A 在大鼠穹窿下器官中的心血管作用。
DOI：
10.1111/j.1365-2826.2006.01497.x
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发表时间：
2007
影响因子：
3.2
通讯作者：
Ferguson,AV
中科院分区：
文献类型：
--
作者：
Smith,PM;Samson,WK;Ferguson,AV
食欲素-A是一种神经肽，主要产生于外侧下丘脑/穹窿周围下丘脑。食欲素受体和免疫反应性神经纤维广泛分布于整个大脑，表明在各种生理系统中的整合神经递质的作用。脑室内注射食欲素A会增加血压并刺激饮酒，而穹窿下器官（SFO）是一种涉及自主控制的室周结构，是食欲素发挥这些作用的潜在部位。因此，我们使用显微注射技术检查了直接给予SFO的食欲素A对氨基甲酸乙酯麻醉的雄性Sprague-道利大鼠血压和心率的影响。SFO内微量注射食欲素A（50 fmol）可导致血压（SFO：平均曲线下面积（AUC） = −681.7 ± 46.8 mmHg*s，n = 22 vs非SFO：63.68 ± 54.69 mmHg*s，n = 15，P <0.001）和心率（SFO：平均AUC = −26.7 ± 2.8次心跳，n = 22 vs非SFO：平均AUC = 1.62 ± 2.1次心跳，n = 15，P <0.001）的部位特异性降低。 迷走神经切断术并没有改变食欲素-A微量注射引起的兴奋或心动过缓反应。先前使用酚苄明（1 mg/kg，i. v.） 掩盖了食欲素A诱导的血压（平均AUC = −122.6 ± 17.6 mmHg*s，n = 4，P <0.01，配对t检验）和心率（平均AUC = −6.7 ± 1.7次，n = 4，P <0.05，配对检验）反应。 当用普萘洛尔（1 mg/kg，i. v.; 平均AUC = 0.6 ± 2.8次心跳，n = 5，P <0.01配对t检验）。 这些研究表明，将食欲素A微量注射到SFO中会导致血压和心率的部位特异性降低，这是由交感神经张力的降低介导的。
Orexin‐A is a neuropeptide, primarily produced in the lateral hypothalamic/perifornical hypothalamus. Orexin receptors and immunoreactive neuronal fibres are widely distributed throughout the brain, suggesting integrative neurotransmitter roles in a variety of physiological systems. Intracerebroventricular injections of orexin‐A increase blood pressure and stimulate drinking, and the subfornical organ (SFO), a circumventricular structure implicated in autonomic control, is a potential site at which orexin may act to exert these effects. We have therefore used microinjection techniques to examine the effects of orexin‐A administered directly into the SFO on blood pressure and heart rate in urethane anaesthetised male Sprague‐Dawley rats. Orexin‐A microinjection (50 fmol) into the SFO caused site‐specific decreases in blood pressure (SFO: mean area under curve (AUC) = −681.7 ± 46.8 mmHg*s, n = 22 versus non‐SFO: 63.68 ± 54.69 mmHg*s, n = 15, P < 0.001), and heart rate (SFO: mean AUC = −26.7 ± 2.8 beats, n = 22, versus non‐SFO: mean AUC = 1.62 ± 2.1 beats, n = 15, P < 0.001). Vagotomy did not alter the hypotensive or bradycardic responses elicited by orexin‐A microinjection. Prior α‐adrenoceptor blockade with phenoxybenzamine (1 mg/kg, i.v.) masked the orexin‐A induced blood pressure (mean AUC = −122.6 ± 17.6 mmHg*s, n = 4, P < 0.01 paired t‐test) and heart rate (mean AUC = −6.7 ± 1.7 beats, n = 4, P < 0.05, paired test) response. The orexin‐A induced heart rate response was attenuated when β‐adrenoceptors were blocked with propranolol (1 mg/kg, i.v.; mean AUC = 0.6 ± 2.8 beats, n = 5, P < 0.01 paired t‐test). These studies demonstrate that microinjection of orexin‐A into the SFO causes site specific decreases in blood pressure and heart rate which is mediated by a reduction in sympathetic tone.