Castillo E F, López R M, Rodríguez-Silverio J, Bobadilla R A, Castillo C
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del IPN, México, DF, México.
Fundam Clin Pharmacol. 1998;12(6):584-9. doi: 10.1111/j.1472-8206.1998.tb00990.x.
The aim of the present study was to assess the role of vascular alpha 1D-adrenoceptors in the sympathetic vasopressor response in vivo. Specifically, we evaluated the effect of a selective alpha 1D-adrenoceptor antagonist, BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4,5)dec ane-7,9- dione 2HCl), on the vasopressor response induced by preganglionic (T7-T9) sympathetic stimulation in the pithed rat. The vasopressor response was dose-dependently sensitive to inhibition by intravenous BMY 7378 (0.1, 0.31, 1 and 3.1 mg/kg), doses of 1 and 3.1 mg/kg being equally effective. Like BMY 7378, 5-methylurapidil (0.1, 0.31, 1 and 3.1 mg/kg) antagonized the vasopressor response to spinal stimulation; doses of 1 and 3.1 mg/kg were also equally effective. In combination experiments, BMY 7378 (1 mg/kg, i.v.) and the alpha 1A-adrenoceptor antagonist, 5-methylurapidil (1 mg/kg, i.v.), showed an additive effect. The present results demonstrate that the alpha 1D-adrenoceptor subtype plays an important role in the pressor response to sympathetic nerve stimulation in the pithed rat, and confirm the participation of the alpha 1A-adrenoceptor subtype in the same response.
本研究的目的是评估血管α1D -肾上腺素能受体在体内交感缩血管反应中的作用。具体而言，我们评估了选择性α1D -肾上腺素能受体拮抗剂BMY 7378（8 - (2 - (4 - (2 - 甲氧基苯基)-1 - 哌嗪基)乙基)-8 - 氮杂螺(4,5)癸烷 - 7,9 - 二酮二盐酸盐）对去脑大鼠节前（T7 - T9）交感神经刺激诱导的缩血管反应的影响。静脉注射BMY 7378（0.1、0.31、1和3.1 mg/kg）可使缩血管反应呈剂量依赖性敏感，1和3.1 mg/kg剂量同样有效。与BMY 7378一样，5 - 甲基尿嘧啶（0.1、0.31、1和3.1 mg/kg）拮抗对脊髓刺激的缩血管反应；1和3.1 mg/kg剂量也同样有效。在联合实验中，BMY 7378（1 mg/kg，静脉注射）和α1A -肾上腺素能受体拮抗剂5 - 甲基尿嘧啶（1 mg/kg，静脉注射）显示出相加作用。目前的结果表明，α1D -肾上腺素能受体亚型在去脑大鼠对交感神经刺激的升压反应中起重要作用，并证实α1A -肾上腺素能受体亚型参与了相同的反应。
