MECHANISMS OF ANGIOTENSIN-INDUCED HYPOTENSION AND BRADYCARDIA IN THE MEDIAL SOLITARY TRACT NUCLEUS
MECHANISMS OF ANGIOTENSIN-INDUCED HYPOTENSION AND BRADYCARDIA IN THE MEDIAL SOLITARY TRACT NUCLEUS
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DOI：
10.1152/ajpheart.1994.267.1.h259
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发表时间：
1994-07-01
影响因子：
--
通讯作者：
BARNES, KL
中科院分区：
文献类型：
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作者：
FOW, JE;AVERILL, DB;BARNES, KL
用选择性血管紧张素Ⅱ（ANG Ⅱ）拮抗剂氯沙坦（losartan，AT（1））和CGP-42112 A（AT（2））研究了麻醉大鼠孤束背内侧核（NTS）或迷走神经背侧运动核（dmnX）微量注射200 fmol ANG Ⅱ引起的低血压和心动过缓的受体亚型和神经通路。在背侧内侧NTS部位（表面以下0.3 mm），其中L-谷氨酸微量注射产生平均动脉压（MAP）和心率（HR）的最大降低，ANG II（200 fmol，50 nl，n = 16）引起低血压（-22 +/- 1 mmHg）和心动过缓（-26 +/- 2次/min）。虽然L-谷氨酸也抑制呼吸，血管紧张素II注射在内侧NTS没有改变呼吸。在NTS内侧注射Losartan可剂量依赖性地降低ANG II诱导的MAP和HR降低。2 pmol时，AT（1）拮抗剂减弱ANG II的反应，而100 pmol则可消除ANG II微量注射的效应。而AT（2）拮抗剂CGP-42112 A（100 pmol）对ANG Ⅱ的反应无影响。ANG II拮抗剂都没有改变L-谷氨酸注射的心血管效应。氯沙坦注射到dmnX阻断低血压和心动过缓所产生的ANG II在该网站，但并没有阻止随后的反应，在内侧NTS的ANG II注射。这些观察结果表明，在背侧延髓中由ANG II诱发的心动过缓和低血压是由AT（1）受体亚型介导的，并确定ANG II在背侧内侧NTS中的心脏抑制作用是由起源于NTS内的神经元机制介导的，而不是由肽扩散到潜在的dmnX中。
The selective angiotensin (ANG) II antagonists losartan (AT(1)) and CGP-42112A (AT(2)) were used to determine the receptor subtype and neuronal pathways that mediate the hypotension and bradycardia produced by 200 fmol of ANG II microinjected into the dorsal medial nucleus tractus solitarii (NTS) or dorsal motor nucleus of the vagus (dmnX) in anesthetized rats. At dorsal medial NTS sites (0.3 mm below the surface) where L-glutamate microinjections produced maximal decreases in mean arterial pressure (MAP) and heart rate (HR), ANG II (200 fmol, 50 nl, n = 16) elicited hypotension (-22 +/- 1 mmHg) and bradycardia (-26 +/- 2 beats/min). Although L-glutamate also suppressed respiration, ANG II injections in the medial NTS did not alter respiration. Losartan injected at the medial NTS site caused a dose-dependent reduction of ANG II-induced decreases in MAP and HR. At 2 pmol, the AT(1) antagonist attenuated the responses to ANG II, whereas 100 pmol abolished the effects of ANG II microinjections. In contrast, the AT(2) antagonist CGP-42112A (100 pmol) had no effect on the responses to ANG II. Neither ANG II antagonist altered the cardiovascular effects of L-glutamate injections. Losartan injected into the dmnX blocked hypotension and bradycardia produced by ANG II at that site but did not prevent responses to subsequent ANG II injections in the medial NTS. These observations reveal that the bradycardia and hypotension evoked by ANG II in the dorsal medulla are mediated by the AT(1)-receptor subtype and establish that the cardioinhibitory effects of ANG II in the dorsal medial NTS are mediated by neuronal mechanisms originating within the NTS rather than by diffusion of the peptide into the underlying dmnX.