Peripheral noradrenergic turnover in streptozotocin-induced diabetic rats

Our goal was to determine whether basal sympathetic tone to the kidney and various peripheral tissues is altered in conscious diabetic rats. Norepinephrine (NE) turnover was determined by measuring the decline in tissue NE concentration ([NE]) at 4 and 8 h after administering α-methyl-p-tyrosine to animals from each of three groups, diabetic (STZ injected 4 weeks prior to experimentation), diabetic + insulin (STZ injected; insulin injected; 2 U/day per rat for 4 weeks) and control (n = 18-20 per group). Various peripheral tissues (duodenum, left ventricle of the heart, kidney, skeletal muscle, left adrenal gland and liver) were examined. [NE] was significantly increased in the kidney and liver, but decreased in the duodenum of the diabetic compared to the control rats. In contrast to the changes in [NE], the rate constant, which provides an index of sympathetic tone, increased in the duodenum and liver, and a decrease in the adrenal gland. The turnover of NE, which is a composite of [NE] and rate constant, increased in the kidney and liver, and decreased in the adrenal gland of diabetic rats. Chronic treatment of diabetic rats with insulin normalized NE turnover in the liver, but not in the adrenal gland. Diabetic rats treated with insulin exhibited a reduced turnover of NE in the kidneys. These data demonstrate that there are differential changes in the [NE], rate constant, and turnover of NE in diabetic rats. Overall, these data indicate that there is increased noradrenergic activity to the kidney, possibly related to sodium retention, and a differential change in noradrenergic activation to various peripheral tissues in diabetic rats.