孤束核微注射内皮素-1对心血管活动的影响

Cardiovascular responses evoked by endothelin 1 microinjected into the nucleus tractus solitarius

目的：研究内皮素１（ＥＴ１）在大鼠孤束核对心血管活动的作用及其机制。方法：麻醉大鼠单侧孤束核微注射ＥＴ１后，观察血压、心率、左室收缩压和ｄｐ／ｄｔｍａｘ以及动脉压力反射敏感性的变化。并观察预先孤束核微注射ＥＴ受体拮抗剂或预先静脉注射神经节阻断剂对ＥＴ１在大鼠孤束核中作用之影响。结果：在乌拉坦麻醉大鼠，单侧孤束核微注射３种剂量（１．０，３．３和１０．０ｐｍｏｌ）的ＥＴ１均可引起血压、左室收缩压和ｄｐ／ｄｔｍａｘ升高，呈剂量依赖性；心率轻度减慢，与剂量不相关；血压持续升高９０ｍｉｎ以上。孤束核微注射选择性ＥＴＡ受体拮抗剂ＰＤ１４７９５３或非选择性ＥＴ受体拮抗剂ＰＤ１４２８９３均不影响血压和心率。预先静脉注射六烃季铵或预先孤束核微注射ＰＤ１４７９５３均可取消外源性ＥＴ１在孤束核的心血管作用。在α氯醛糖麻醉大鼠，孤束核微注射ＥＴ１（３．３ｐｍｏｌ）可显著抑制动脉压力感受性反射。结论：内皮素１通过孤束核ＥＴＡ受体参与心血管活动的中枢调控，但不起张力性作用；该调节作用依赖自主神经系统。

Objective: To study the role of endothelin 1 (ET 1), a potent vasoconstrictor originally isolated from vascular endothelial cells, within the nucleus tractus solitarius (NTS) in central cardiovascular control. Methods: To observe the changes in blood pressure, heart rate, left ventricular systolic pressure and ±dp/dt max , and arterial baroreflex sensitivity after a unilateral microinjection of ET 1 into the NTS of anesthetized rats, and observe whether these changes could be inhibited by preinjection of ET antagonists into the NTS or by intravenous pretreatment with a ganglionic blocker. Results: In urethane anesthetized rats, a unilateral microinjection of ET 1 (1.0, 3.3, 10.0 pmol) into the NTS significantly increased arterial pressure, left ventricular systolic pressure and ±dp/dt max in a dose dependent manner,and slightly decreased heart rate in a non dose dependent manner. The pressor response lasted more than 90 min. Neither PD147953, a selective ET A receptor antagonist, nor PD142893, a mixed ET A and ET B receptor antagonist, micro injected into the NTS elicited any changes in arterial pressure or heart rate. The pressor and bradycardiac effects evoked by a microinjection of ET 1 into the NTS could be blocked by local pretreatment with PD142893, and completely eliminated by intravenous pretreatment with ganglionic blocker hexamethonium. The arterial baroreflex sensitivity was almost totally suppressed by a microinjection of ET 1 (3.3 pmol) in α chloralose anesthetized rats. Conclusion: ET 1 modulates reflex control of hemodynamics by activation of autonomic nerve via ET A receptors in the NTS.