Nosjean A, Callera J C, Bonagamba L, Machado B, Hamon M, Laguzzi R
INSERM U288, NeuroPsychoPharmacologie, Faculté de Médecine Pitié-Salpêtrière, 75634 Paris Cedex 13, France.
Neuroscience. 2002;112(4):935-49. doi: 10.1016/s0306-4522(02)00057-x.
The present study was performed to determine whether or not the increased arterial pressure triggered by 5-HT(3) receptor stimulation in the nucleus tractus solitarii and underlain by a sympathoexcitation is associated with the activation of ventromedullary cells known to be involved in vascular regulation, i.e. the C1 and A1 catecholaminergic cells. For this purpose, double immunohistochemical labeling for tyrosine hydroxylase and c-fos protein was performed all along the ventrolateral medulla after microinjection of 1-(m-chlorophenyl)-biguanide, a selective and potent 5-HT(3) receptor agonist, into the nucleus tractus solitarii of alpha-chloralose/urethane-anaesthetized rats. This treatment produced a significant elevation of arterial pressure ( approximately +35 mm Hg). Concomitantly, a significant increase in the number of c-fos expressing neurons was observed in the rostral ventrolateral medulla (+63%), in particular in its most anterior part (+78%), and in the medullary region surrounding the caudal part of the facial nucleus (+91%). Retrograde labeling with gold-horseradish peroxidase complex showed that at least some of these activated c-fos expressing cells project to the spinal cord. However, the number of double-stained neurons, i.e. c-fos and tyrosine hydroxylase positive neurons, did not increase at any level of the ventrolateral medulla. In contrast, under the same alpha-chloralose/urethane anesthesia, systemic infusion of sodium nitroprusside appeared to produce a hypotension and a marked increase in the density of such double c-fos and tyrosine hydroxylase expressing cells in the rostral ventrolateral medulla and the caudal medullary region surrounding the caudal part of the facial nucleus. These data indicate that medullary catecholaminergic C1 and A1 neurons are not involved in the pressor effect elicited by 5-HT(3) receptor stimulation in the nucleus tractus solitarii. However, this 5-HT(3) receptor-mediated effect is clearly associated with the excitation of (non-catecholaminergic) neurons within the pressor region of the ventral medulla.
本研究旨在确定孤束核中5-HT(3)受体刺激引发的、由交感神经兴奋介导的动脉血压升高是否与已知参与血管调节的腹侧髓质细胞（即C1和A1儿茶酚胺能细胞）的激活有关。为此，在α-氯醛糖/乌拉坦麻醉的大鼠孤束核中微量注射1-(间氯苯基)双胍（一种选择性强效5-HT(3)受体激动剂）后，沿腹外侧髓质进行酪氨酸羟化酶和c-fos蛋白的双重免疫组织化学标记。该处理使动脉血压显著升高（约+35 mmHg）。同时，在延髓头端腹外侧（增加63%），特别是其最前部（增加78%）以及面神经核尾侧周围的髓质区域（增加91%）观察到c-fos表达神经元数量显著增加。用金-辣根过氧化物酶复合物进行逆行标记显示，这些激活的c-fos表达细胞中至少有一些投射到脊髓。然而，腹外侧髓质任何水平的双染神经元（即c-fos和酪氨酸羟化酶阳性神经元）数量均未增加。相反，在相同的α-氯醛糖/乌拉坦麻醉下，硝普钠全身输注似乎导致血压降低，并使延髓头端腹外侧和面神经核尾侧周围的尾侧髓质区域中这种c-fos和酪氨酸羟化酶双表达细胞的密度显著增加。这些数据表明，延髓儿茶酚胺能C1和A1神经元不参与孤束核中5-HT(3)受体刺激引发的升压效应。然而，这种5-HT(3)受体介导的效应显然与腹侧髓质升压区域内（非儿茶酚胺能）神经元的兴奋有关。
