Abdel-Rahman A R
Department of Pharmacology, East Carolina University School of Medicine, Greenville, N.C. 27858.
Arch Int Pharmacodyn Ther. 1989 Jan-Feb;297:68-85.
The ability of hexamethonium (HEX) alone or in combination with atropine methylbromide (AMB) to block the heart rate (HR) response to baroreceptor activation by phenylephrine (PE) or angiotensin II (AII)-evoked increments in blood pressure was evaluated in rats. A highly significant negative correlation existed under control conditions between the changes in MAP and HR. HEX (10-20 mg/kg) did not influence the baroreceptor HR response of anesthetized and conscious rats, suggesting anesthesia was not involved in the failure of HEX to abolish the baroreceptor HR response. A combination of HEX and AMB (full ganglionic blockade) substantially attenuated but did not abolish the HR response to baroreceptor activation, but this effect was not significantly different from that produced by AMB alone. In a marked contrast to HEX, chlorisondamine (CHL) abolished the baroreceptor HR response both in anesthetized and in conscious rats. Efficacy of ganglionic blockade was tested by examining the effects of HEX or CHL on the frequency-bradycardic response relationship evoked by electrical stimulation of the peripheral end of the right vagus; HEX only attenuated the response whereas CHL abolished it. It is concluded that, even in doses which lower blood pressure, HEX: 1) does not adequately block the baroreceptor HR response; 2) when combined with a muscarinic blocker to induce full ganglionic blockade, the decrease in baroreceptor HR response is largely, if not totally, attributable to muscarinic blockade; 3) is much weaker than CHL in blocking ganglionic transmission and, even when combined with a muscarinic blocker, it does not abolish the baroreceptor HR response whereas CHL does, and 4) CHL represents a better choice for studies that require complete ganglionic blockade in anesthetized or conscious rats.
在大鼠中评估了六甲铵（HEX）单独或与甲基溴化阿托品（AMB）联合使用时，对去氧肾上腺素（PE）或血管紧张素II（AII）诱发的血压升高所引起的压力感受器激活导致的心率（HR）反应的阻断能力。在对照条件下，平均动脉压（MAP）变化与HR之间存在高度显著的负相关。HEX（10 - 20mg/kg）不影响麻醉和清醒大鼠的压力感受器HR反应，这表明麻醉并非HEX未能消除压力感受器HR反应的原因。HEX与AMB联合使用（完全神经节阻断）可显著减弱但并未消除对压力感受器激活的HR反应，但其效果与单独使用AMB所产生的效果并无显著差异。与HEX形成鲜明对比的是，氯异吲哚胺（CHL）在麻醉和清醒大鼠中均消除了压力感受器HR反应。通过检查HEX或CHL对电刺激右迷走神经外周端诱发的频率 - 心动过缓反应关系的影响来测试神经节阻断的效果；HEX仅减弱反应，而CHL则消除了该反应。得出的结论是，即使在降低血压的剂量下，HEX：1）不能充分阻断压力感受器HR反应；2）当与毒蕈碱阻断剂联合使用以诱导完全神经节阻断时，压力感受器HR反应的降低即使不是完全，也主要归因于毒蕈碱阻断；3）在阻断神经节传递方面比CHL弱得多，即使与毒蕈碱阻断剂联合使用，它也不能消除压力感受器HR反应，而CHL可以；4）对于需要在麻醉或清醒大鼠中进行完全神经节阻断的研究，CHL是更好的选择。
