Couture R, Hasséssian H, Gupta A
Département de Physiologie, CRSN, Faculté de Médecine, Université de Montréal, Québec, Canada.
J Cardiovasc Pharmacol. 1988 Mar;11(3):270-83. doi: 10.1097/00005344-198803000-00003.
Administration of 6.5-pmol-6.5-nmol doses of substance P (SP) into the spinal subarachnoid space at T-8-T-10 in urethane-anesthetized rats increases both mean arterial pressure (MAP) and heart rate (HR) in a dose-related manner. However, in rats anesthetized with sodium pentobarbital, an increase in MAP is seen only at low doses of SP (6.5-65 pmol), while a biphasic response is obtained at 650 pmol and only a depressor response at 6.5 nmol SP. These responses also are accompanied by a tachycardia. Depending on the spinal cord level, cardiovascular responses of different time course and magnitude are elicited by SP. The amplitude of the increases in MAP and HR produced by SP (6.5 nmol) are: T-8-T-10 greater than T-1-T-3 greater than L-2-L-4 in rats anesthetized with urethane. In rats anesthetized with sodium pentobarbital, the decrease in MAP levels is greatest at T-1-T-3, while it is similar at T-8-T-10 and L-2-L-4 levels. The effects of SP on HR are more complex. The different cardiovascular responses obtained with the two anesthetics are not attributed to the relative depth of anesthesia but may be due to differential effects of the anesthetics on sympathetic nervous activity. The effect of SP on HR can be blocked by propranolol, but it remains unaffected by the surgical removal of the adrenal glands. We conclude that this cardiovascular response is most likely mediated by the postganglionic noradrenergic fibres and that adrenal medullary catecholamines are not essential. Using several inhibitors of endogenous mediators, two components to the spinal action of SP on MAP are made evident. The pressor response can be explained solely by the activation of sympathetic preganglionic fibres in the intermediolateral nucleus of the spinal cord, while the depressor response, in addition, may involve the release of a vasodilatatory substance in the periphery, the action of which persists in the presence of cholinergic, histaminergic, serotonergic, or opioid antagonists. Moreover, the adrenal glands are excluded as a possible source of this substance.
在氨基甲酸乙酯麻醉的大鼠中，于T-8至T-10水平向脊髓蛛网膜下腔注射6.5皮摩尔至6.5纳摩尔剂量的P物质（SP），可使平均动脉压（MAP）和心率（HR）均呈剂量依赖性增加。然而，在戊巴比妥钠麻醉的大鼠中，仅在低剂量SP（6.5至65皮摩尔）时可见MAP升高，而在650皮摩尔时获得双相反应，在6.5纳摩尔SP时仅出现降压反应。这些反应也伴有心动过速。根据脊髓水平的不同，SP可引发不同时程和幅度的心血管反应。在氨基甲酸乙酯麻醉的大鼠中，SP（6.5纳摩尔）引起的MAP和HR升高幅度为：T-8至T-10大于T-1至T-3大于L-2至L-4。在戊巴比妥钠麻醉的大鼠中，MAP水平的降低在T-1至T-3时最大，而在T-8至T-10和L-2至L-4水平时相似。SP对HR的影响更为复杂。两种麻醉剂所获得的不同心血管反应并非归因于麻醉的相对深度，而可能是由于麻醉剂对交感神经活动的不同作用。SP对HR的作用可被普萘洛尔阻断，但不受肾上腺手术摘除的影响。我们得出结论，这种心血管反应很可能由节后去甲肾上腺素能纤维介导，肾上腺髓质儿茶酚胺并非必需。使用几种内源性介质抑制剂后，SP对MAP的脊髓作用可明显分为两个成分。升压反应可仅通过脊髓中间外侧核中交感神经节前纤维的激活来解释，而降压反应此外可能涉及外周血管舒张物质的释放，其作用在胆碱能、组胺能、5-羟色胺能或阿片类拮抗剂存在时依然持续。此外，肾上腺被排除为该物质的可能来源。
