Relation of Blood Pressure Quantitative Trait Locus on Rat Chromosome 1 to Hyperactivity of Rostralventrolateral Medulla
Relation of Blood Pressure Quantitative Trait Locus on Rat Chromosome 1 to Hyperactivity of Rostralventrolateral Medulla
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DOI：
10.1161/hypertensionaha.108.117804
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发表时间：
2009-01-01
期刊：
影响因子：
8.3
通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Iigaya, Kamon;Kumagai, Hiroo;Itoh, Hiroshi
使用全基因组连锁分析研究了诱发原发性高血压的遗传因素。在易卒中的自发性高血压大鼠（SHRSPs）1号染色体上发现了一个与高血压密切相关的数量性状位点（QTL）。本研究利用2只同源大鼠，通过反复回交，将1号染色体上的血压QTL从SHRSP/Izm（WKY）/Izm（WKYpch1.0）和从WKY/Izm（WKY）/Izm（SHRSP/Izm）（SHRSPwch1.0）大鼠中进行了基因渗入。以往的研究报道，该QTL的中间表型的高血压的特征是交感神经系统的过度活跃，以响应生理和心理应激。我们进行了细胞内膜片钳记录头端腹外侧延髓（RVLM）神经元从WKY，WKYpch1.0，SHRSPwch1.0，SHRSPs和比较的基础电生理活动的RVLM神经元和这些神经元的反应，血管紧张素II。来自WKYpch1.0的RVLM神经元的基底膜电位比来自WKY的神经元的基底膜电位显著“浅”。WKYpch1.0的RVLM神经元对血管紧张素II的反应性去极化显著大于WKY大鼠，而SHRSPwch1.0的RVLM神经元对血管紧张素II的反应性去极化显著小于SHRSPs。血管紧张素II的RVLM神经元从WKYpch1.0和SHRSPs的反应持续，即使在所有的突触传递使用河豚毒素的封锁。大鼠1号染色体上的QTL主要与RVLM球脊髓神经元对脑血管紧张素II的突触后反应相关，而该QTL和其他基因组区域都影响RVLM神经元的基础活性。（高血压。2009; 53：42-48.）
Genetic factors that induce essential hypertension have been examined using genome-wide linkage analyses. A quantitative trait locus (QTL) region that is closely linked to hypertension has been found on chromosome 1 in stroke-prone spontaneously hypertensive rats (SHRSPs). We used 2 congenic rats in which the blood pressure QTL on rat chromosome 1 was introgressed from SHRSP/Izm to Wistar-Kyoto (WKY)/Izm (WKYpch1.0) and from WKY/Izm to SHRSP/Izm (SHRSPwch1.0) rats by repeated backcrossing. Previous studies reported that the intermediate phenotype of this QTL for hypertension is characterized by the hyperactivity of the sympathetic nervous system in response to physiological and psychological stress. We performed intracellular patch-clamp recordings of rostral ventrolateral medulla (RVLM) neurons from WKY, WKYpch1.0, SHRSPwch1.0, and SHRSPs and compared the basal electrophysiological activities of RVLM neurons and the responses of these neurons to angiotensin II. The basal membrane potential of RVLM neurons from WKYpch1.0 was significantly "shallower" than that of the neurons from WKY. The depolarization of RVLM neurons from WKYpch1.0 in response to angiotensin II was significantly larger than that in neurons from WKY rats, whereas the depolarization of RVLM neurons from SHRSPwch1.0 was significantly smaller than that in neurons from SHRSPs. The response to angiotensin II of RVLM neurons from WKYpch1.0 and SHRSPs was sustained even after the blockade of all of the synaptic transmissions using tetrodotoxin. The QTL on rat chromosome 1 was primarily related to the postsynaptic response of RVLM bulbospinal neurons to brain angiotensin II, whereas both the QTL and other genomic regions influenced the basal activity of RVLM neurons. (Hypertension. 2009; 53: 42-48.)