Huvers F C, de Leeuw P W, de Haan C H, Houben A J, Buijs C, Schaper N C
Dept. of Internal Medicine, Cardiovascular Research Institute Maastricht, University Hospital Maastricht, Netherlands.
Cardiovasc Res. 1998 Apr;38(1):206-14. doi: 10.1016/s0008-6363(97)00319-2.
The present study was performed to discriminate between central and peripheral effects of noradrenaline (NA) in normotensive, non-obese, type 2 diabetic patients.
Study I: In 10 patients and 10 healthy volunteer (HV) cumulative doses of NA were infused intravenously until mean arterial pressure (MAP) rose with 20 mmHg, and subsequently the effects on the forearm blood flow (FBF) was measured. Also, the FBF response to intra-arterial NA (0.025, 0.1, 0.4 micrograms min-1) was measured. Study II: In 13 patients and 14 HV the venous constrictor response to a cumulative local infusion of NA in a dorsal hand vein was determined.
In study I the circulating plasma NA concentrations inducing a rise in MAP of 20 mmHg, were lower in the type 2 patients relative to the HV (p < 0.01). The relationship between changes in pressure and changes in heart rate were similar in both groups. Moreover, FBF responsiveness to intra-arterial NA was not different between the two groups. The slopes of the delta MAP/NA regression lines were correlated with basal insulin levels and relative insulin resistance in the healthy volunteers (R = 0.77, p < 0.01, and R = 0.83, p < 0.01), but not in the type 2 diabetic patients. In study II no differences were observed in the dose generating half maximum (ED50) and the maximum (Emax) response to NA between the type 2 patients and the HV.
Non-obese normotensive type 2 patients have an increased pressor response to NA, which is not based upon a defect in skeletal muscle resistance arterioles, peripheral veins, or a defect in the baroreceptor system. Therefore, in type 2 diabetes the noradrenergic responsiveness of other vascular beds, such as the splanchnic or renal, must be enhanced.
本研究旨在区分去甲肾上腺素（NA）在血压正常、非肥胖2型糖尿病患者中的中枢和外周作用。
研究I：对10例患者和10名健康志愿者（HV）静脉输注累积剂量的NA，直至平均动脉压（MAP）升高20 mmHg，随后测量对前臂血流量（FBF）的影响。此外，还测量了动脉内注射NA（0.025、0.1、0.4微克/分钟）时的FBF反应。研究II：对13例患者和14名HV，测定在手背静脉中累积局部输注NA时的静脉收缩反应。
在研究I中，使MAP升高20 mmHg的循环血浆NA浓度，2型患者低于HV（p < 0.01）。两组压力变化与心率变化之间的关系相似。此外，两组对动脉内NA的FBF反应性无差异。健康志愿者中，δMAP/NA回归线的斜率与基础胰岛素水平和相对胰岛素抵抗相关（R = 0.77，p < 0.01，以及R = 0.83，p < 0.01），但在2型糖尿病患者中无相关性。在研究II中，2型患者与HV之间，产生半数最大效应的剂量（ED50）和对NA的最大（Emax）反应未观察到差异。
非肥胖血压正常的2型患者对NA的升压反应增强，这并非基于骨骼肌阻力小动脉、外周静脉的缺陷或压力感受器系统的缺陷。因此，在2型糖尿病中，其他血管床（如内脏或肾脏）的去甲肾上腺素能反应性必定增强。
