Renal sympathetic nerve discharge mediated by the paraventricular nucleus is altered in STZ induced diabetic rats.

Abstract

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.