Simultaneous parasympathetic and sympathetic activation reveals altered autonomic control of heart rate, vascular tension, and epinephrine release in anesthetized hypertensive rats.
Simultaneous parasympathetic and sympathetic activation reveals altered autonomic control of heart rate, vascular tension, and epinephrine release in anesthetized hypertensive rats.
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DOI：
10.3389/fneur.2011.00071
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发表时间：
2011
影响因子：
3.4
通讯作者：
Jensen J
中科院分区：
文献类型：
--
作者：
Berg T;Jensen J
交感神经功能亢进和副交感神经功能不全是遗传性高血压患者血压控制的特征。这种转变在麻醉大鼠中很难研究。在这里，我们提出了一种药理学方法，同时引起交感神经和副交感神经递质释放，并确定其各自的作用，伴随心血管反应。为了刺激麻醉的正常血压大鼠（WKY）和自发性高血压大鼠（SHR）的递质释放，我们静脉注射了电压敏感性K+通道（KV）抑制剂4-氨基吡啶（4-AP）。股动脉导管监测血压，升主动脉流量探头记录心输出量和心率（HR）。计算总外周血管阻力（TPVR）。4-AP诱导的立即，阿托品（毒蕈碱拮抗剂）和六甲铵（神经节阻滞剂）敏感性心动过缓WKY，并在两个菌株，随后，持续的心动过速，去甲肾上腺素，但不是肾上腺素释放。利血平（交感神经阻滞剂）、纳多洛尔（β-肾上腺素能受体拮抗剂）或右迷走神经刺激可消除迟发性心动过速，肾上腺切除术、东莨菪碱（中枢毒蕈碱拮抗剂）或六烃季铵不能消除迟发性心动过速。4-AP增加TPVR，在WKY短暂，但在SHR持续。育亨宾（α 2-肾上腺素能受体拮抗剂）可抑制WKY TPVR的下调。利血平和哌唑嗪（α 1-肾上腺素能受体拮抗剂）可消除SHR迟发性血管收缩。血浆肾上腺素溢出增加纳多洛尔治疗的SHR。通过抑制KV，4-AP激活副交感神经节传递和外周神经元去甲肾上腺素释放。交感神经成分在自发性高血压（SHR）的4-AP-HR反应中占主导地位。在WKY中，α 2-肾上腺素能受体依赖性血管舒张对抗去甲肾上腺素诱导的α 1-肾上腺素能血管收缩，但在SHR中则不然。A β AR可能通过迷走神经传入机制抑制SHR肾上腺素分泌。因此，4-AP激活了自主神经系统，并揭示了与高血压疾病相关的机制。
Sympathetic hyperactivity and parasympathetic insufficiency characterize blood pressure (BP) control in genetic hypertension. This shift is difficult to investigate in anesthetized rats. Here we present a pharmacological approach to simultaneously provoke sympathetic and parasympathetic transmitter release, and identify their respective roles in the concomitant cardiovascular response. To stimulate transmitter release in anesthetized normotensive (WKY) and spontaneously hypertensive rats (SHR), we injected intravenously 4-aminopyridine (4-AP), a voltage-sensitive K+ channel (KV) inhibitor. A femoral artery catheter monitored BP, an ascending aorta flow-probe recorded cardiac output and heart rate (HR). Total peripheral vascular resistance (TPVR) was calculated. 4-AP-induced an immediate, atropine (muscarinic antagonist)- and hexamethonium (ganglion blocker)-sensitive bradycardia in WKY, and in both strains, a subsequent, sustained tachycardia, and norepinephrine but not epinephrine release. Reserpine (sympatholytic), nadolol (β-adrenoceptor antagonist) or right vagal nerve stimulation eliminated the late tachycardia, adrenalectomy, scopolamine (central muscarinic antagonist) or hexamethonium did not. 4-AP increased TPVR, transiently in WKY but sustained in SHR. Yohimbine (α2-adrenoceptor antagonist) prevented the TPVR down-regulation in WKY. Reserpine and prazosin (α1-adrenoceptor antagonist) eliminated the late vasoconstriction in SHR. Plasma epinephrine overflow increased in nadolol-treated SHR. Through inhibition of KV, 4-AP activated parasympathetic ganglion transmission and peripheral, neuronal norepinephrine release. The sympathetic component dominated the 4-AP–HR-response in SHR. α2-adrenoceptor-dependent vasodilatation opposed norepinephrine-induced α1-adrenergic vasoconstriction in WKY, but not SHR. A βAR-activated, probably vagal afferent mechanism, hampered epinephrine secretion in SHR. Thus, 4-AP activated the autonomic system and exposed mechanisms relevant to hypertensive disease.