Australian School of Advanced Medicine, Macquarie Univ., NSW 2109, Australia.
Am J Physiol Regul Integr Comp Physiol. 2010 Dec;299(6):R1538-45. doi: 10.1152/ajpregu.00335.2010. Epub 2010 Oct 6.
The fundamental role and corollary effects of neuropeptides that govern cardiorespiratory control in the brain stem are poorly understood. One such regulatory peptide, catestatin [Cts, human chromogranin A-(352-372)], noncompetitively inhibits nicotinic-cholinergic-stimulated catecholamine release. Previously, we demonstrated the presence of chromogranin A mRNA in brain stem neurons that are important for the maintenance of arterial pressure. In the present study, using immunofluorescence histochemistry, we show that Cts immunoreactivity is colocalized with tyrosine hydroxylase in C1 neurons of the rostral ventrolateral medulla (RVLM, n = 3). Furthermore, we investigated the effects of Cts on resting blood pressure, splanchnic sympathetic nerve activity, phrenic nerve activity, heart rate, and adaptive reflexes. Cts (1 mM in 50 nl or 100 μM in 50-100 nl) was microinjected into the RVLM in urethane-anesthetized, vagotomized, ventilated Sprague-Dawley rats (n = 19). Cardiovascular responses to stimulation of carotid baroreceptors, peripheral chemoreceptors, and the sciatic nerve (somatosympathetic reflex) were analyzed. Cts (1 mM in 50 nl) increased resting arterial pressure (28 ± 3 mmHg at 2 min postinjection), sympathetic nerve activity (15 ± 3% at 2 min postinjection), and phrenic discharge amplitude (31 ± 4% at 10 min postinjection). Cts increased sympathetic barosensitivity 40% (slope increased from -0.05 ± 0.01 before Cts to -0.07 ± 0.01 after Cts) and attenuated the somatosympathetic reflex [1st peak: 36% (from 132 ± 32.1 to 84.0 ± 17.0 μV); 2nd peak: 44% (from 65.1 ± 21.4 to 36.6 ± 14.1 μV)] and chemoreflex (blood pressure response to anoxia decreased 55%, sympathetic response decreased 46%). The results suggest that Cts activates sympathoexcitatory bulbospinal neurons in the RVLM and plays an important regulatory role in adaptive reflexes.
神经肽在脑干中对心肺控制的基本作用和必然影响还没有被充分理解。一种这样的调节肽，Cts（人类嗜铬粒蛋白 A-（352-372）），非竞争性地抑制烟碱型胆碱能刺激儿茶酚胺的释放。先前，我们证明了脑干部位的神经元中存在嗜铬粒蛋白 A mRNA，这些神经元对维持动脉血压很重要。在本研究中，我们使用免疫荧光组织化学方法，显示 Cts 免疫反应性与延髓头端腹外侧区（RVLM，n = 3）C1 神经元中的酪氨酸羟化酶共定位。此外，我们还研究了 Cts 对静息血压、内脏交感神经活动、膈神经活动、心率和适应性反射的影响。在乌拉坦麻醉、迷走神经切断、通气的 Sprague-Dawley 大鼠的 RVLM 中（n = 19），用微量注射器注入 Cts（50 nl 中的 1 mM 或 50-100 nl 中的 100 μM）。分析颈动脉压力感受器、外周化学感受器和坐骨神经（躯体交感反射）刺激引起的心血管反应。Cts（50 nl 中的 1 mM）在注射后 2 分钟时增加静息动脉血压（增加 28 ± 3 mmHg）、交感神经活动（增加 15 ± 3%）和膈神经放电幅度（增加 31 ± 4%）。Cts 使交感神经压力敏感性增加 40%（斜率从 Cts 前的-0.05 ± 0.01 增加到 Cts 后的-0.07 ± 0.01），并减弱了躯体交感反射[第 1 峰：36%（从 132 ± 32.1 增加到 84.0 ± 17.0 μV）；第 2 峰：44%（从 65.1 ± 21.4 增加到 36.6 ± 14.1 μV）]和化学反射（缺氧时血压反应降低 55%，交感反应降低 46%）。结果表明，Cts 激活 RVLM 中的交感兴奋延髓脊髓神经元，并在适应性反射中发挥重要的调节作用。
