Sesoko S, Muratani H, Yamazato M, Teruya H, Takishita S, Fukiyama K
Third Department of Internal Medicine, University of The Ryukyus School of Medicine, Okinawa, Japan.
Am J Physiol. 1998 Apr;274(4):R1119-24. doi: 10.1152/ajpregu.1998.274.4.R1119.
The inhibitory action of alpha 2-agonists on the cardiovascular neurons has been elucidated in the rostral ventrolateral medulla (RVLM) but not in the caudal ventrolateral medulla (CVLM). Our study aimed to clarify whether microinjection of clonidine into the CVLM elicits any cardiovascular effect and whether endogenous alpha 2-adrenoceptor-mediated mechanisms contribute to the tonic activity of the CVLM neurons. In male Sprague-Dawley rats (7-9 wk old, 270-320 g) anesthetized with urethan, unilateral microinjection of 8 nmol of clonidine into the CVLM (n = 10) increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) by 12.1 +/- 1.8 mmHg (mean +/- SE, P < 0.01) and 25.8 +/- 4.8% (P < 0.01), while heart rate (HR) remained unaltered. Unilateral microinjection of 2 nmol of SKF-86466, a selective blocker of the alpha 2-adrenoceptors, into the CVLM (n = 10) decreased MAP, HR, and RSNA (-11.6 +/- 2.6 mmHg, -26 +/- 7 beats/min, and -15.3 +/- 1.7%, respectively, P < 0.01 for each). Artificial cerebrospinal fluid caused neither a cardiovascular effect nor a sympathetic response. Prior injection of SKF-86466 into the ipsilateral CVLM attenuated the effects of clonidine. Bilateral microinjection of muscimol into the RVLM abolished the effects of both clonidine and SKF-86466 injected into the CVLM. The pressor and sympathoexcitatory effects of clonidine injected into the CVLM suggest a neuroinhibitory action of the drug on the CVLM neurons. In addition, the depressor and sympathoinhibitory effects of SKF-86466 injected into the CVLM indicated that activation of alpha 2-adrenoceptors by endogenous ligand inhibits CVLM neurons. The effects of clonidine and the alpha 2-adrenoceptor antagonist in the CVLM require the integrity of the RVLM.
α₂ 激动剂对心血管神经元的抑制作用已在延髓头端腹外侧区（RVLM）得到阐明，但在延髓尾端腹外侧区（CVLM）尚未明确。我们的研究旨在明确向 CVLM 微量注射可乐定是否会引发任何心血管效应，以及内源性 α₂ 肾上腺素能受体介导的机制是否参与 CVLM 神经元的紧张性活动。在使用乌拉坦麻醉的雄性 Sprague-Dawley 大鼠（7 - 9 周龄，270 - 320 g）中，向 CVLM 单侧微量注射 8 nmol 可乐定（n = 10）使平均动脉压（MAP）和肾交感神经活动（RSNA）分别升高 12.1 ± 1.8 mmHg（平均值 ± 标准误，P < 0.01）和 25.8 ± 4.8%（P < 0.01），而心率（HR）保持不变。向 CVLM 单侧微量注射 2 nmol 的 SKF - 86466（一种 α₂ 肾上腺素能受体的选择性阻滞剂，n = 10）使 MAP、HR 和 RSNA 降低（分别为 -11.6 ± 2.6 mmHg、-26 ± 7 次/分钟和 -15.3 ± 1.7%，每项 P < 0.01）。人工脑脊液既未引起心血管效应，也未引发交感反应。事先向同侧 CVLM 注射 SKF - 86466 可减弱可乐定的作用。向 RVLM 双侧微量注射蝇蕈醇可消除向 CVLM 注射可乐定和 SKF - 86466 的效应。向 CVLM 注射可乐定的升压和交感兴奋作用表明该药物对 CVLM 神经元具有神经抑制作用。此外，向 CVLM 注射 SKF - 86466 的降压和交感抑制作用表明内源性配体激活 α₂ 肾上腺素能受体可抑制 CVLM 神经元。可乐定和 α₂ 肾上腺素能受体拮抗剂在 CVLM 中的作用需要 RVLM 的完整性。
