Department of Nephrology and Endocrinology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Department of Physiology, Showa University School of Medicine, Tokyo, Japan.
Hypertens Res. 2014 Nov;37(11):976-83. doi: 10.1038/hr.2014.112. Epub 2014 Jun 26.
The expression and effects of β-adrenergic receptors (β-ARs) on the neurons of the bulbospinal rostral ventrolateral medulla (RVLM) have been limitedly examined to date. The objective of this study was to examine the expression of β1- and β2-ARs on the bulbospinal RVLM neurons electrophysiologically and histologically. To directly investigate whether RVLM neurons display sensitivity to metoprolol (a β1-AR antagonist), dobutamine (a β1-AR agonist), butoxamine (a β2-AR antagonist), and salbutamol (a β2-AR agonist), we examined changes in the membrane potentials of the bulbospinal RVLM neurons using the whole-cell patch-clamp technique during superfusion of these drugs. During metoprolol superfusion, 16 of the 20 RVLM neurons were hyperpolarized, and 5 of the 6 RVLM neurons were depolarized during dobutamine superfusion. During butoxamine superfusion, 11 of the 16 RVLM neurons were depolarized, and all of the 8 RVLM neurons were hyperpolarized during salbutamol superfusion. These results suggest the expression of β1- and β2-ARs on the RVLM neurons. To determine the presence of β1- and β2-ARs histologically, immunofluorescence examination was performed. Five metoprolol-hyperpolarized neurons were examined for β1-AR and tyrosine hydroxylase (TH) immunoreactivity. All of the neurons displayed β1-AR immunoreactivity, whereas three of the neurons displayed TH immunoreactivity. All of the five RVLM neurons that became depolarized during metoprolol superfusion and hyperpolarized during butoxamine superfusion displayed β1- and β2-AR immunoreactivity. Our findings suggest that β1-AR antagonists or β2-AR agonists may decrease blood pressure through decreasing the activity of the bulbospinal RVLM neurons.
迄今为止，人们对延髓头端腹外侧区（RVLM）的神经元中β-肾上腺素能受体（β-ARs）的表达和作用研究有限。本研究旨在通过电生理学和组织学方法研究β1-和β2-AR 在延髓 RVLM 神经元上的表达。为了直接研究 RVLM 神经元是否对美托洛尔（β1-AR 拮抗剂）、多巴酚丁胺（β1-AR 激动剂）、布他沙明（β2-AR 拮抗剂）和沙丁胺醇（β2-AR 激动剂）敏感，我们使用全细胞膜片钳技术，在这些药物灌流期间观察 RVLM 神经元的膜电位变化。在美托洛尔灌流期间，20 个 RVLM 神经元中有 16 个被超极化，在多巴酚丁胺灌流期间，6 个 RVLM 神经元中有 5 个被去极化。在布他沙明灌流期间，16 个 RVLM 神经元中有 11 个被去极化，在沙丁胺醇灌流期间，8 个 RVLM 神经元全部被超极化。这些结果表明 RVLM 神经元表达β1-和β2-AR。为了从组织学上确定β1-和β2-AR 的存在，我们进行了免疫荧光检查。对 5 个被美托洛尔超极化的神经元进行了β1-AR 和酪氨酸羟化酶（TH）免疫反应性检测。所有神经元均显示β1-AR 免疫反应性，其中 3 个神经元显示 TH 免疫反应性。在美托洛尔灌流时去极化、布他沙明灌流时超极化的 5 个 RVLM 神经元均显示β1-和β2-AR 免疫反应性。我们的发现表明，β1-AR 拮抗剂或β2-AR 激动剂可能通过降低 RVLM 神经元的活性来降低血压。
