Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Boulevard Venustiano Carranza esquina con Ing. José Cárdenas Valdés, Colonia República, C.P. 25280 Saltillo, Coahuila, Mexico.
Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Boulevard Venustiano Carranza esquina con Ing. José Cárdenas Valdés, Colonia República, C.P. 25280 Saltillo, Coahuila, Mexico.
Eur J Pharmacol. 2017 Jun 15;805:75-83. doi: 10.1016/j.ejphar.2017.03.009. Epub 2017 Mar 14.
This study has investigated the role of the α-adrenoceptor subtypes involved in the inhibition of the cardiac sympathetic outflow induced by intravenous (i.v) infusions of agmatine. Therefore, we analysed the effect of an i.v. bolus injections of the selective antagonists BRL 44408 (300μg/kg; α), imiloxan (3000μg/kg; α), and JP-1302 (300μg/kg; α) given separately, and their combinations: BRL 44408 plus Imiloxan, JP 1302 plus imiloxan, BRL 44408 plus JP-1302, BRL 44408 plus imiloxan plus JP-1302 on the cardiac sympatho-inhibition of agmatine. Also, the effect of the combination BRL 44408 plus JP-1302 plus AGN 192403 (3000μg/kg; I antagonist) was evaluated. In this way, i.v. infusions of 1000μg/kg min of agmatine, but not 300, inhibited the tachycardic response induced by electrical stimulation. Furthermore, the antagonists used or their combinations had no effect on the electrically-induced tachycardic response. On the other hand, the inhibitory response of agmatine was: (1) partially antagonized by BRL 44408 or JP-1302 given separately, a similar response was observed when we administered their combination with imiloxan, but not by imiloxan alone, (2) antagonized in greater magnitude by the combination BRL 44408 plus JP-1302 or the combination BRL 44408 plus imiloxan plus JP-1302, and (3) abolished by the combination BRL 44408 plus JP-1302 plus AGN 192403. Taken together, these results demonstrate that the α- and α-adrenoceptor subtypes and I-imidazoline receptors are involved in the inhibition of the cardiac sympathetic outflow induced by agmatine.
本研究探讨了静脉输注胍丁胺（agmatine）抑制心脏交感神经输出时涉及的α-肾上腺素受体亚型的作用。因此，我们分析了静脉推注选择性拮抗剂 BRL 44408（300μg/kg；α）、伊米洛坦（3000μg/kg；α）和 JP-1302（300μg/kg；α）的作用，以及它们的组合：BRL 44408 加伊米洛坦、JP 1302 加伊米洛坦、BRL 44408 加 JP-1302、BRL 44408 加伊米洛坦加 JP-1302 对胍丁胺抑制心脏交感神经的影响。此外，还评估了组合 BRL 44408 加 JP-1302 加 AGN 192403（3000μg/kg；I 拮抗剂）的效果。静脉输注 1000μg/kg·min 的胍丁胺可抑制电刺激引起的心动过速反应，但输注 300μg/kg·min 的胍丁胺则无此作用。此外，上述拮抗剂或其组合对电刺激引起的心动过速反应无影响。另一方面，胍丁胺的抑制反应为：（1）BRL 44408 或 JP-1302 单独给药时部分拮抗，与伊米洛坦联合给药时观察到类似反应，但伊米洛坦单独给药时则无此反应；（2）BRL 44408 加 JP-1302 或 BRL 44408 加伊米洛坦加 JP-1302 的联合给药可显著拮抗，（3）BRL 44408 加 JP-1302 加 AGN 192403 的联合给药可完全拮抗。综上所述，这些结果表明，α-和α-肾上腺素受体亚型以及 I-咪唑啉受体参与了胍丁胺抑制心脏交感神经输出的过程。
