Mechanism of cyclosporine-induced sympathetic activation and acute hypertension in rats.
Mechanism of cyclosporine-induced sympathetic activation and acute hypertension in rats.
复制标题
环孢素诱导大鼠交感神经激活和急性高血压的机制。
DOI：
10.1161/01.hyp.23.5.667
复制
发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Victor,RG
中科院分区：
文献类型：
--
作者：
Lyson,T;McMullan,DM;Ermel,LD;Morgan,BJ;Victor,RG
虽然静脉注射环孢素A(CsA)已被证明能引起大鼠交感神经调节的血压升高，但CsA增加交感神经系统活动的潜在机制尚不清楚。为了确定中枢神经和外周反射机制在引起交感神经激活中的相对作用，我们记录了侧脑室内或静脉注射环孢素A时的传出肾交感神经活动和血压，后者在正常大鼠和去窦弓神经、颈迷走神经或膈下迷走神经切断术或背根切断术(T10至L1)的大鼠中进行。在正常大鼠中，静脉注射CsA(5 mg/kg)，如预期的那样，使肾交感神经活动增加两倍，平均动脉压增加27+/-4 mm Hg(P<；0.05)。新的发现是：静脉注射CsA的这种交感兴奋效应不能通过中枢给药(进入脑室系统或直接进入延髓的腹外侧面)复制，(2)不受去窦弓神经的影响，但(3)经颈迷走神经或横隔膜下迷走神经切断术或背根切断术显著减弱。在其他实验中，我们发现静脉注射环孢素增加了隔下传入的多单位活动，但不增加心肺迷走神经传入的多单位活动。根据这些数据，我们得出结论，在环孢素A诱导的大鼠交感神经活动和血压的增加主要是由于兴奋的神经反射出现在横隔膜下区域。这些反射机制至少使用两条不同的传入神经通路：一条涉及膈下迷走神经，另一条涉及下胸背根。
Although intravenous cyclosporine A (CsA) previously has been shown to cause a robust sympathetically mediated increase in blood pressure in the rat, the underlying mechanism by which CsA increases the activity of the sympathetic nervous system is unknown. To determine the relative contributions of central neural versus peripheral reflex mechanisms in causing this sympathetic activation, we recorded efferent renal sympathetic nerve activity and blood pressure during intracerebroventricular or intravenous infusion of CsA, the latter performed in intact rats and in those with sinoaortic denervation, cervical or subdiaphragmatic vagotomy, or dorsal rhizotomy (T10 through L1). In intact rats, intravenous CsA (5 mg/kg), as expected, tripled renal sympathetic nerve activity and increased mean arterial pressure by 27 +/- 4 mm Hg (P < .05). The new findings are that this sympathoexcitatory effect of intravenous CsA (1) was not duplicated by central administration (either into the cerebroventricular system or directly onto the ventrolateral surface of the medulla), (2) was unaffected by sinoaortic denervation, but (3) was greatly attenuated by either cervical or subdiaphragmatic vagotomy or by dorsal rhizotomy. In additional experiments, we found that intravenous cyclosporine increased the multiunit activity of subdiaphragmatic but not cardiopulmonary vagal afferents. From these data, we conclude that in the rat CsA-induced increases in sympathetic activity and blood pressure are caused mainly by activation of excitatory neural reflexes arising in the subdiaphragmatic region. These reflex mechanisms use at least two different afferent neural pathways: one involving the subdiaphragmatic vagi and the other involving the low thoracic dorsal spinal roots.