Clinical Pharmacology Unit, Vargas Medical School, Central University of Venezuela, Caracas, Venezuela.
Am J Ther. 2010 May-Jun;17(3):320-4. doi: 10.1097/MJT.0b013e3181c1232c.
The objective is to determine cardiovascular and insulin release effects under metoclopramide (MTC) and dopamine (DA) infusion by using an acute comparative design with the intravenous infusion of both drugs. We evaluated 15 normal (normotensive and normoglycemic) subjects, 13 hypertensive, and 15 type 2 diabetic subjects. Subjects were submitted to an experimental design in which we first gave them a 0.9% saline solution for 30 minutes, and then administered MTC at 7.5 microg kg min through an intravenous infusion during a period of 30 minutes. Although subjects were receiving MTC, we added an intravenous infusion of DA at 1-3 microg kg min during 30 minutes. Blood pressure, heart rate, serum lipid profile, and insulin levels were measured. Sympathetic reactivity by the cold pressor test was also measured. In normotensive subjects, there was a systolic blood pressure and heart rate increase during MTC plus DA infusion. In subjects with diabetes mellitus there was a heart rate increase without changes in blood pressure during the MTC plus DA infusion period. In hypertensive subjects, MTC induced a significant decrease of systolic and diastolic blood pressure. During MTC plus DA period there was an increase of heart rate but no significant changes in blood pressure. During cold pressor test in both diabetic and hypertensive subjects, there were significant increases of both blood pressure and heart rate. Insulin serum levels increased in normotensive and hypertensive subjects but were attenuated in subjects with diabetes mellitus. We conclude that there is a pharmacologic interaction between MTC and DA, that the pressor effects of DA are due to activation to beta and alpha adrenergic receptors, and that the cardiovascular effects of DA in type 2 diabetic subjects are attenuated by a probable defect in sympathetic system and to endothelial dysfunction.
目的是通过使用静脉内输注两种药物的急性比较设计，确定甲氧氯普胺（MTC）和多巴胺（DA）输注下的心血管和胰岛素释放效应。我们评估了 15 名正常（血压正常和血糖正常）受试者、13 名高血压患者和 15 名 2 型糖尿病患者。受试者接受了实验设计，我们首先给他们输注 0.9%生理盐水 30 分钟，然后在 30 分钟内通过静脉输注给予 MTC 7.5μg/kg/min。虽然受试者正在接受 MTC，但我们在 30 分钟内以 1-3μg/kg/min 的速度静脉输注 DA。测量血压、心率、血清脂质谱和胰岛素水平。还测量了冷加压试验的交感神经反应。在血压正常的受试者中，MTC 加 DA 输注期间出现收缩压和心率升高。在糖尿病患者中，MTC 加 DA 输注期间心率增加而血压无变化。在高血压患者中，MTC 引起收缩压和舒张压显著降低。在 MTC 加 DA 期间，心率增加，但血压无显著变化。在糖尿病和高血压患者的冷加压试验中，血压和心率均显著升高。MTC 加 DA 期间，正常血压和高血压受试者的血清胰岛素水平升高，但糖尿病患者的血清胰岛素水平减弱。我们的结论是，MTC 和 DA 之间存在药理相互作用，DA 的升压作用归因于β和α肾上腺素能受体的激活，DA 在 2 型糖尿病患者中的心血管作用被交感神经系统和内皮功能障碍的可能缺陷所减弱。
