Analysis of afferent, central, and efferent components of the baroreceptor reflex in mice

Analysis of afferent, central, and efferent components of the baroreceptor reflex in mice
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DOI:
10.1152/ajpregu.00768.2001
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发表时间:
2002-11-01
影响因子:
2.8
通讯作者:
Chapleau, MW
Chapleau, MW
中科院分区:
医学3区
文献类型:
--
作者:
Ma, XY;Abboud, FM;Chapleau, MW

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转基因小鼠的研究为研究生理和病理状态下基因表达改变的后果提供了强有力的方法。本研究的目的是表征麻醉Webster 4小鼠压力感受器反射的传入、中枢和传出成分。通过测量肾交感神经活性(RSNA)和主动脉降压神经活性(ADNA)对硝普塞和苯肾上腺素引起的动脉压变化的反应来表征压力反射和压力感受器传入功能。数据拟合为s型logistic函数曲线。压反射舒张压阈值(P-th)、RSNA抑制50%时的压力(P-mid)和压反射增益(最大斜率)平均分别为74 +/- 5mmhg、101 +/- 3mmhg和2.30 +/- 0.54%/mmHg (n = 6)。舒张压- adna关系(压力感受器传入)的P-th、P-mid和增益与整体反射平均79 +/- 9mmhg、101 +/- 4mmhg和2.92 +/- 0.53%/mmHg相似(n = 5)。通过分别记录左ADN和右迷走神经末梢对电刺激的反应,分别评估中枢神经系统对压力反射的调节和心脏对迷走神经传出活动的变时性反应。ADN和迷走神经传出刺激均诱导频率依赖性心率和动脉压降低。戊巴比妥钠麻醉小鼠(n = 4)与氯胺酮-乙酰丙嗪麻醉小鼠(n = 4)相比,ADN刺激的心率反应几乎消失,而迷走神经传出刺激在两种麻醉下的反应是相同的。将这些技术应用于转基因小鼠的研究,可用于识别压力反射功能的分子机制,并将改变的功能定位于传入、中枢或传出部位。
Studies of genetically modified mice provide a powerful approach to investigate consequences of altered gene expression in physiological and pathological states. The goal of the present study was to characterize afferent, central, and efferent components of the baroreceptor reflex in anesthetized Webster 4 mice. Baroreflex and baroreceptor afferent functions were characterized by measuring changes in renal sympathetic nerve activity (RSNA) and aortic depressor nerve activity (ADNA) in response to nitroprusside- and phenylephrine-induced changes in arterial pressure. The data were fit to a sigmoidal logistic function curve. Baroreflex diastolic pressure threshold (P-th), the pressure at 50% inhibition of RSNA (P-mid), and baroreflex gain (maximum slope) averaged 74 +/- 5 mmHg, 101 +/- 3 mmHg, and 2.30 +/- 0.54%/mmHg, respectively (n = 6). The P-th, P-mid, and gain for the diastolic pressure-ADNA relation (baroreceptor afferents) were similar to that observed for the overall reflex averaging 79 +/- 9 mmHg, 101 +/- 4 mmHg, and 2.92 +/- 0.53%/mmHg, respectively (n = 5). The central nervous system mediation of the baroreflex and the chronotropic responsiveness of the heart to vagal efferent activity were independently assessed by recording responses to electrical stimulation of the left ADN and the peripheral end of the right vagus nerve, respectively. Both ADN and vagal efferent stimulation induced frequency-dependent decreases in heart rate and arterial pressure. The heart rate response to ADN stimulation was nearly abolished in mice anesthetized with pentobarbital sodium (n = 4) compared with mice anesthetized with ketamine-acepromazine (n = 4), whereas the response to vagal efferent stimulation was equivalent under both types of anesthesia. Application of these techniques to studies of genetically manipulated mice can be used to identify molecular mechanisms of baroreflex function and to localize altered function to afferent, central, or efferent sites.