Caligiorne S M, Santos R A, Campagnole-Santos M J
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Brain Res. 1996 May 13;720(1-2):183-90. doi: 10.1016/0006-8993(95)01498-5.
In this study, we characterized the cardiovascular effects produced by microinjection of doses in the femtomole range of bradykinin (BK) into the nucleus tractus solitarii of male Wistar rats (230-280 g, n = 120) anesthetized with urethane (1.2 g/kg, i.p.). Microinjections of BK (1, 10, 100 fmol, and 1 and 10 pmol, in 50 nl) or vehicle (NaCl, 0.9%) were made by using a triple-barreled glass micropipette into the medial nTS (0.4 mm anterior, 0.3 mm lateral to the obex and 0.3 mm deep from the dorsal surface). Microinjection of BK produced a shallow dose-dependent decrease in mean arterial pressure and heart rate reaching -18 +/- 6 mmHg and -21 +/- 5 beats/min, with the dose of 10 pmol. The peripheral mechanism of these effects, tested in animals treated with methylatropine (2 mg/kg, i.v.), or propranolol (2 mg/kg, i.v.) or prazosin (30 micrograms/kg, i.v.), was shown to be mainly dependent on an increase in vagal efferent activity for bradycardia and a decrease in sympathetic activity for hypotension. In order to investigate the receptor subtype involved in these effects, BK was microinjected into the nTS before and after the injection of the B1 receptor antagonist, Des-Arg9-Leu8-BK (DALBK) (11.5 pmol) or before and after the B2 receptor antagonist, HOE-140 (7.7 pmol). The cardiovascular effects of BK were significantly attenuated by the microinjection of HOE-140 and DALBK into the nTS. The effect of BK microinjected into the nTS on the baroreflex modulation was also investigated. While BK produced a significant facilitation of the baroreflex, HOE-140 and DALBK produced a significant attenuation of the baroreceptor control of heart rate. Taken together, the data presented in this study indicate the nTS as a site, in the central nervous system, for the modulatory effect of BK on the central cardiovascular control.
在本研究中,我们对用氨基甲酸乙酯(1.2 g/kg,腹腔注射)麻醉的雄性Wistar大鼠(230 - 280 g,n = 120)孤束核内微量注射飞摩尔剂量的缓激肽(BK)所产生的心血管效应进行了表征。使用三管玻璃微量移液器将BK(1、10、100飞摩尔以及1和10皮摩尔,50纳升)或溶剂(0.9%氯化钠)微量注射到内侧孤束核(在闩前方0.4毫米、闩外侧0.3毫米以及背表面下方0.3毫米处)。微量注射BK会使平均动脉压和心率呈浅剂量依赖性下降,在注射10皮摩尔剂量时分别达到 - 18 ± 6 mmHg和 - 21 ± 5次/分钟。在用甲基阿托品(2 mg/kg,静脉注射)、普萘洛尔(2 mg/kg,静脉注射)或哌唑嗪(30微克/千克,静脉注射)处理的动物中测试这些效应的外周机制,结果表明其主要依赖于迷走神经传出活动增加导致心动过缓以及交感神经活动减少导致低血压。为了研究参与这些效应的受体亚型,在注射B1受体拮抗剂去精氨酸 - 亮氨酸 - 缓激肽(DALBK)(11.5皮摩尔)之前和之后或B2受体拮抗剂HOE - 140(7.7皮摩尔)之前和之后,将BK微量注射到孤束核中。向孤束核内微量注射HOE - 140和DALBK可显著减弱BK的心血管效应。还研究了微量注射到孤束核中的BK对压力反射调节的影响。虽然BK显著促进了压力反射,但HOE - 140和DALBK显著减弱了压力感受器对心率的控制。综上所述,本研究呈现的数据表明孤束核是中枢神经系统中BK对中枢心血管控制起调节作用的位点。