El-Mas M M, Abdel-Rahman A A
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, U.S.A.
Neuroscience. 1997 Jul;79(2):581-90. doi: 10.1016/s0306-4522(96)00648-3.
Earlier findings have shown that alpha2-adrenoceptors in the nucleus tractus solitarius and rostral ventrolateral medulla modulate baroreflexes. The present study investigated whether attenuation of baroreflexes induced by surgical interruption of aortic baroafferents is related to an alteration of alpha2-adrenoceptor binding in these regions of the brainstem. In vitro autoradiography was utilized to assess the density and binding dissociation constant (affinity) of alpha2-adrenoceptors in the rostral ventrolateral medulla and in the middle and rostral portions of the nucleus tractus solitarius of aortic-barodenervated and sham-operated rats. Compared to sham operation, aortic barodenervation caused an acute rise in mean arterial pressure and heart rate and a significant reduction in baroreflex sensitivity. Two days later, mean arterial pressure and heart rate of conscious aortic-barodenervated rats subsided to sham-operated levels, whereas the baroreflex sensitivity remained significantly (P<0.05) reduced when measured by phenylephrine (0.55+/-0.08 vs 1.26+/-0.07 ms/mmHg) or nitroprusside (0.43+/-0.06 vs 1.01+/-0.09ms/mmHg). Examination of brainstem coronal sections obtained from separate groups of rats 48 h after surgery and preincubated with [3H]rauwolscine (0.5-16 nM) revealed that labeling of alpha2 binding sites was saturable and of high affinity. Scatchard analysis of the saturation isotherms obtained from the three brain areas of sham-operated rats showed an uneven distribution of alpha2 binding sites; the rostral nucleus tractus solitarius exhibited the highest density and lowest affinity. Aortic barodenervation caused region-dependent changes in the binding activity of alpha2-adrenoceptors. These changes comprised significant (P<0.05) increases in the density of alpha2-adrenoceptors in the middle nucleus tractus solitarius (436+/-60 vs 240+/-50 fmol/mg protein) and rostral ventrolateral medulla (350+/-67 vs 194+/-35 fmol/mg protein) compared with sham-operated rats; no significant changes occurred in the rostral nucleus tractus solitarius. The affinity of alpha2 binding sites was not changed by aortic barodenervation in any of the three brain regions. These findings suggest that attenuation of baroreflexes produced by aortic barodenervation coincides with up-regulation of alpha2-adrenoceptors in brainstem areas that play critical roles in the control of cardiovascular functions.
早期研究结果表明，孤束核和延髓头端腹外侧区的α2肾上腺素能受体可调节压力感受性反射。本研究调查了主动脉压力感受器传入神经手术切断所诱导的压力感受性反射减弱是否与脑干这些区域中α2肾上腺素能受体结合的改变有关。利用体外放射自显影技术评估主动脉去神经支配大鼠和假手术大鼠延髓头端腹外侧区以及孤束核中部和头端部分中α2肾上腺素能受体的密度和结合解离常数（亲和力）。与假手术相比，主动脉去神经支配导致平均动脉压和心率急性升高，压力感受性反射敏感性显著降低。两天后，清醒的主动脉去神经支配大鼠的平均动脉压和心率降至假手术水平，而当用去氧肾上腺素（0.55±0.08对1.26±0.07毫秒/毫米汞柱）或硝普钠（0.43±0.06对1.01±0.09毫秒/毫米汞柱）测量时，压力感受性反射敏感性仍显著降低（P<0.05）。对术后48小时从不同组大鼠获取并预先用[3H]萝芙木碱（0.5 - 16纳摩尔）孵育的脑干冠状切片进行检查发现，α2结合位点的标记是可饱和的且具有高亲和力。对假手术大鼠三个脑区获得的饱和等温线进行Scatchard分析显示，α2结合位点分布不均；孤束核头端密度最高且亲和力最低。主动脉去神经支配导致α2肾上腺素能受体的结合活性出现区域依赖性变化。这些变化包括与假手术大鼠相比，孤束核中部（436±60对240±50飞摩尔/毫克蛋白）和延髓头端腹外侧区（350±67对194±35飞摩尔/毫克蛋白）中α2肾上腺素能受体密度显著增加（P<0.05）；孤束核头端未发生显著变化。在三个脑区中的任何一个，主动脉去神经支配均未改变α2结合位点的亲和力。这些发现表明，主动脉去神经支配所产生的压力感受性反射减弱与在心血管功能控制中起关键作用的脑干区域中α2肾上腺素能受体的上调相一致。
