Comparison of cardiac control mechanism of nucleus ambiguus of the medulla in hypertensive and normotensive rats

神經控制機制在短期與長期的血壓調節上扮演著相當重要的角色。在高血壓形成過程中，不管是在年輕的病人或自發性高血壓大鼠(spontaneously hypertensive rat, SHR)中均發現有交感神經活性(activity)或反應性(reactivity)異常偏高的現象。但是許多文獻也顯示SHR感壓反射能力受損，其降心跳反應明顯減弱，血管的調節能力則無異常，因此探討高血壓大鼠中，與交感神經相拮抗的副交感神經活性與反應性是否發生異常，實有其必要性。 本研究利用SHR(12-16週齡)為高血壓模式動物並以其同齡近親正常血壓之WKY (Wistar-Kyoto) rat及一般的Wistar rat為對照組，來探討高血壓動物控制心臟的副交感神經系統是否產生異常。以不同劑量的麩胺酸(10 mM L-glutamate, Glu)注射於大鼠延腦的疑核(nucleus ambiguus)，進行降心跳反應的劑量－反應實驗，來比較三種大鼠延腦副交感神經機構之反應性，並且分析刺激位置的神經元放電型態。實驗結果發現，雖然三種大鼠的最大降心跳反應與閾值劑量沒有統計上的差異，但是有趨勢顯示SHR所需的閾值劑量與飽和劑量均較大。而且造成最大降心跳反應的飽和劑量在SHR中明顯大於Wistar rat；劑量－反應曲線的斜率則以Wistar rat為最大。由實驗結果推測，SHR的疑核可能對麩胺酸刺激的反應性變低，需要較大的刺激才會引起最大的降心跳反應。在三種大鼠的疑核中，大多數神經元具有呼吸節律的放電活性，具有心跳節律的神經元活性極少。Neurogenic mechanisms play a key role in both rapid and long-term regulations of blood pressure (BP). It is believed that enhanced sympathetic activity and reactivity are major factors contributing to the essential hypertension. Previous evidences suggested that cardiac but not vascular component of the baroreflex of the spontaneously hypertensive rat (SHR) was significantly less sensitive than that of normotensive rat. It is of interest to determine whether the cardiac vagal preganglionic neurons (CVPNs), which counteracts with sympathetic system, exhibit higher or lower reactivity. In the present study, the HR responses to glutamate solution (Glu) stimulation of the CVPNs in nucleus ambiguus (NA) of the 12-16 week old SHR were compared with aged matched normotensive WKY (Wistar-Kyoto) rats and Wistar rats. Microinjection of different doses of 10 mM Glu into the NA produced dose-dependent responses of heart rate (HR) in normotensive and hypertensive rats. The maximal HR changes and threshold dose of Glu were not significantly different in three strains, but there was a tendency that the threshold dose of SHR was largest, then that of WKY rats and Wistar rats. The saturation dose of Glu to elicit the maximal HR change was also significantly larger in SHR than that in Wistar rats. The maximal slope of dose-response curve in Wistar rats is steepest in three strains. The results suggested that the reactivity of CVPNs in NA to Glu stimulation might be lower in SHR than that in Wistar rats. Most neurons in NA had respiratory firing patterns, few pulse-related neurons were observed in three strains of rats.中文摘要……………………………………………………………………………..1 Abstracts……………………………………………………………………………...2 1. Introduction………………………………………………………………………...3 1.1 Cardiovascular control nuclei in medulla……………………….…………..3 1.2 Parasympathetic control of the heart……………………….……………….4 1.3 Nucleus ambiguus……………………………………………………………5 1.4 Spontaneously hypertensive rat……………………………………………..5 1.5 The sympathetic activity of SHR…………………………………………...6 1.6 The parasympathetic activity in SHR……….………………………………7 1.7 Baroreflex sensitivity in SHR………………………………………………8 1.8 Goals of this study………………………………………………………….8 2. Materials and methods…………………………………………………………….10 2.1 Animals……………………………………………………………………10 2.2 General preparation……………………………………………………..…10 2.3 Construction of injection-recording microelectrode………………………11 2.4 Unit activity recording and medullary glutamate stimulation…………….11 2.5 Histology…………………………………………………………………..12 2.6 Data analysis………………………………………………………………13 2.6.1 Dose-response curve…………………………………………………13 2.6.2 Unit firing pattern analysis………………………………………...13 2.6.3 Statistics……………………………………………………………14 3. Results……………………………………………………………………………..15 3.1 Bradycardiac response to Glu stimulation of NA………………………....15 3.2 The firing patterns of unit activities……………………………………….17 4. Discussion…………………………………………………………………………19 4.1 The bradycardiac effect of NA stimulation………………………………..19 4.2 The unit activities in cardiovascular area of NA…………………………..20 4.3 The difference of NA activity between normotensive and hypertensive rats.21 4.4 Technical comments and future works…………………….………………22 5. References…………………………………………………………………………24 6. Tables………………………………………………………………………………31 7. Figures……………………………………………………………………………..3