Reynolds A Y, Zhang K, Patel K P
Department of Physiology & Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
Nebr Med J. 1996 Dec;81(12):419-23.
The purpose of this study was to determine if the renal sympathetic nerve discharge (RSND), mediated by the paraventricular nucleus of the hypothalamus (PVN), is altered in streptozotocin (STZ) induced diabetic rats. Two to three weeks prior to the start of the experiment the diabetic group was treated with a single injection of STZ (65 mg/kg ip) in a 2% solution of cold 0.1 M citrate buffer (pH = 4.5). The control group was injected with the vehicle alone. Bicuculline (BIC) was injected into the PVN in three different doses (0.5, 1.0 & 2.0 nmol) while the RSND was being monitored. BIC is an antagonist of gamma-aminobutyric acid (GABA) which is an inhibitory neurotransmitter that is thought to exert a tonic inhibitory effect on the PVN. Microinjection of BIC produced a significantly lower response of RSND in the diabetic group compared to the control group. Microinjection of BIC produced a 13, 35 and 33% change in RSND in diabetic rats compared to control group in response to 0.5, 1.0, and 2.0 nmol doses, respectively. Mean blood pressure and heart rate were statistically not different between the control and the diabetic groups. However there were tendencies of the blood pressure and heart rate to be blunted upon injection of BIC into PVN in diabetic rats. This study demonstrates that RSND in response to microinjection of BIC in PVN is decreased significantly in anesthetized diabetic rats, indicating that STZ induced diabetic rats have a blunted RSND response to microinjection of BIC. There is also some evidence, although not statistically significant, for a blunted blood pressure and heart rate were diabetics. These findings suggest that there is a reduced endogenous inhibitory influence of GABAergic mechanisms within the PVN involved in regulating renal sympathetic outflow in the diabetic state.
本研究的目的是确定由下丘脑室旁核（PVN）介导的肾交感神经放电（RSND）在链脲佐菌素（STZ）诱导的糖尿病大鼠中是否发生改变。在实验开始前两到三周，糖尿病组用2%冷0.1M柠檬酸盐缓冲液（pH = 4.5）中的单次注射STZ（65mg/kg腹腔注射）进行治疗。对照组仅注射赋形剂。在监测RSND的同时，将荷包牡丹碱（BIC）以三种不同剂量（0.5、1.0和2.0nmol）注入PVN。BIC是γ-氨基丁酸（GABA）的拮抗剂，GABA是一种抑制性神经递质，被认为对PVN发挥紧张性抑制作用。与对照组相比，微量注射BIC在糖尿病组中产生的RSND反应明显更低。与对照组相比，微量注射BIC在糖尿病大鼠中分别对0.用5、1.0和2.0nmol剂量产生的RSND变化为13%、35%和33%。对照组和糖尿病组之间的平均血压和心率在统计学上没有差异。然而，在糖尿病大鼠中向PVN注射BIC后，血压和心率有变钝的趋势。本研究表明，在麻醉的糖尿病大鼠中，对PVN微量注射BIC的RSND反应显著降低，表明STZ诱导的糖尿病大鼠对微量注射BIC的RSND反应迟钝。也有一些证据表明糖尿病患者的血压和心率变钝，尽管在统计学上不显著。这些发现表明，在糖尿病状态下，参与调节肾交感神经流出的PVN内GABA能机制的内源性抑制作用降低。
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