Nagahama S, Chen Y F, Lindheimer M D, Oparil S
J Pharmacol Exp Ther. 1986 Mar;236(3):735-42.
Administration of LY171555, a specific dopamine D2 receptor agonist, (10-1000 micrograms/kg i.v.) produced dose-related increases in mean arterial pressure in conscious Sprague-Dawley rats. Pretreatment with metoclopramide (5 mg/kg i.v.) abolished the pressor action of LY171555, whereas pretreatment with domperidone (2.5 mg/kg i.v.) and propranolol (10 mg/kg i.p.) did not affect the pressor action of LY171555. The vasopressor antagonist of arginine vasopressin (AVP), d(CH2)5Tyr(Me)AVP (10 micrograms/kg i.v.) and phenoxybenzamine (1 mg/kg i.v.) partly blocked and hexamethonium (25 mg/kg i.v.) enhanced the pressor action of LY171555. After combined treatment with both d(CH2)5Tyr(Me)AVP and phenoxybenzamine, LY171555 induced a depressor response which was completely blocked by pretreatment with domperidone. LY171555 administration induced a rapid, short-acting depressor response followed by a pressor response in conscious adrenomedullectomized Sprague-Dawley rats which was smaller in magnitude than that seen in intact Sprague-Dawley rats. LY171555 administration increased plasma norepinephrine, epinephrine and AVP in conscious Sprague-Dawley rats. These results suggest that the pressor action of LY171555 in conscious rats is dependent on activation of sympathetic outflow and AVP release through the central D2 dopaminergic system and that the central pressor effects of LY171555 could mask a depressor effect of LY171555 at the peripheral D2 dopamine receptor.
给清醒的斯普拉格 - 道利大鼠静脉注射特定的多巴胺D2受体激动剂LY171555（10 - 1000微克/千克），可使平均动脉压出现剂量相关的升高。静脉注射甲氧氯普胺（5毫克/千克）预处理可消除LY171555的升压作用，而静脉注射多潘立酮（2.5毫克/千克）和腹腔注射普萘洛尔（10毫克/千克）预处理则不影响LY171555的升压作用。精氨酸加压素（AVP）的血管升压拮抗剂d(CH2)5Tyr(Me)AVP（10微克/千克静脉注射）和酚苄明（1毫克/千克静脉注射）可部分阻断LY171555的升压作用，而六甲铵（25毫克/千克静脉注射）则增强其升压作用。在联合使用d(CH2)5Tyr(Me)AVP和酚苄明进行治疗后，LY171555诱导出降压反应，该反应可被多潘立酮预处理完全阻断。给清醒的肾上腺切除的斯普拉格 - 道利大鼠注射LY171555会先引起快速、短效的降压反应，随后出现升压反应，但其升压幅度小于完整的斯普拉格 - 道利大鼠。给清醒的斯普拉格 - 道利大鼠注射LY171555会使血浆去甲肾上腺素、肾上腺素和AVP升高。这些结果表明，LY171555在清醒大鼠中的升压作用依赖于通过中枢D2多巴胺能系统激活交感神经传出和AVP释放，并且LY171555的中枢升压作用可能掩盖其在外周D2多巴胺受体上的降压作用。
