Pazos A, Wiederhold K H, Palacios J M
Eur J Pharmacol. 1986 Jun 5;125(1):63-70. doi: 10.1016/0014-2999(86)90083-x.
The cardiovascular effects induced in the rat by several muscarinic receptor agonists were studied. All the agonists produced a clear decrease in heart rate. This decrease appeared to be peripherally mediated, because it was antagonized by methylscopolamine. The effects on blood pressure varied depending on the presence of anaesthesia, previous treatments and the type of agonists tested. When peripheral muscarinic activity was blocked by administration of methylscopolamine, a dose-dependent hypertension was obtained following the injection of oxotremorine, arecoline and aceclidine, by both intraperitoneal and intracerebroventricular routes. The muscarinic receptor agonist RS 86 produced a slight increase in blood pressure but the increase was weaker than those observed with the agonists cited above. On the other hand, the muscarinic receptor agonists pilocarpine, AF-30 and McN-A-343, considered as partially M1-selective compounds, did not produce any effect on blood pressure. Moreover, the hypertension induced by oxotremorine was completely blocked by intracerebroventricular administration of the non-subtype-selective muscarinic receptor antagonist scopolamine but was unaffected by the M1-selective antagonist pirenzepine. We propose that the central hypertensive response induced by muscarinic receptor agonists in the unanaesthetized rat is, at least partially, mediated through the stimulation of the so-called M2 muscarinic receptor subtype.
研究了几种毒蕈碱受体激动剂对大鼠心血管系统的影响。所有激动剂均使心率明显降低。这种降低似乎是由外周介导的，因为它可被甲基东莨菪碱拮抗。对血压的影响因麻醉状态、先前处理以及所测试激动剂的类型而异。当通过给予甲基东莨菪碱阻断外周毒蕈碱活性时，通过腹腔注射和脑室内注射氧震颤素、槟榔碱和醋甲胆碱均可获得剂量依赖性高血压。毒蕈碱受体激动剂RS 86使血压略有升高，但升高幅度弱于上述激动剂。另一方面，被认为是部分M1选择性化合物的毒蕈碱受体激动剂毛果芸香碱、AF - 30和McN - A - 343对血压没有任何影响。此外，脑室内注射非亚型选择性毒蕈碱受体拮抗剂东莨菪碱可完全阻断氧震颤素诱导的高血压，但不受M1选择性拮抗剂哌仑西平的影响。我们认为，未麻醉大鼠中毒蕈碱受体激动剂诱导的中枢性高血压反应至少部分是通过刺激所谓的M2毒蕈碱受体亚型介导的。
