Tsukamoto K, Yin M, Sved A F
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
Brain Res. 1994 Jun 13;648(1):9-15. doi: 10.1016/0006-8993(94)91898-8.
Previous experiments have demonstrated that stimulation of muscarinic cholinergic receptors in the nucleus tractus solitarius (NTS) of the rat decreases arterial blood pressure and heart rate. The present studies were designed to examine the role of cholinergic mechanisms in the NTS in the tonic regulation of arterial pressure and the baroreceptor reflex. Atropine injected into the NTS of chloralose-anesthetized rats produced a dose-dependent inhibition of cardiovascular responses elicited by injection of acetylcholine into the same site; 240 pmol atropine eliminated acetylcholine-evoked responses. Atropine also increased arterial blood pressure but only at higher doses. Even larger doses of atropine were required to alter cardiovascular responses elicited by electrical stimulation of the aortic depressor nerve. Methylatropine injected into the NTS also blocked acetylcholine-evoked responses but, in contrast to the actions of atropine, did not increase arterial pressure in the dose range required to block acetylcholine-evoked responses. Furthermore, a dose of methylatropine (1 nmol) capable of blocking acetylcholine-evoked cardiovascular responses did not alter aortic depressor nerve-evoked cardiovascular responses. This lack of an effect of methylatropine on arterial pressure and aortic depressor nerve-evoked responses was not due to limited diffusion of the drug within the NTS since 1 nmol methylatropine completely blocked acetylcholine-evoked responses even when injected 0.5 mm distant from the site of acetylcholine injection. These results suggest that cholinergic mechanisms in the NTS are not involved in the tonic regulation of cardiovascular function or the baroreceptor reflex. Furthermore, these results highlight the importance of characterizing doses of drugs used in microinjection studies.
先前的实验表明,刺激大鼠孤束核(NTS)中的毒蕈碱胆碱能受体会降低动脉血压和心率。本研究旨在探讨NTS中胆碱能机制在动脉血压的紧张性调节和压力感受器反射中的作用。向用氯醛糖麻醉的大鼠的NTS中注射阿托品,可对向同一部位注射乙酰胆碱所引发的心血管反应产生剂量依赖性抑制;240皮摩尔阿托品可消除乙酰胆碱诱发的反应。阿托品还会升高动脉血压,但仅在较高剂量时才会出现。需要更大剂量的阿托品才能改变由电刺激主动脉减压神经所引发的心血管反应。向NTS中注射甲基阿托品也能阻断乙酰胆碱诱发的反应,但与阿托品的作用相反,在阻断乙酰胆碱诱发反应所需的剂量范围内,甲基阿托品不会升高动脉血压。此外,一剂能够阻断乙酰胆碱诱发的心血管反应的甲基阿托品(1纳摩尔)并不会改变由主动脉减压神经诱发的心血管反应。甲基阿托品对动脉血压和主动脉减压神经诱发反应缺乏作用,并非由于药物在NTS内的扩散受限,因为即使在距离乙酰胆碱注射部位0.5毫米处注射1纳摩尔甲基阿托品,也能完全阻断乙酰胆碱诱发的反应。这些结果表明,NTS中的胆碱能机制不参与心血管功能的紧张性调节或压力感受器反射。此外,这些结果凸显了在微量注射研究中确定所用药物剂量的重要性。