Noradrenergic mechanisms in the brain and peripheral organs of normotensive and spontaneously hypertensive rats at various ages.

Abstract

Previous studies of noradrenergic mechanisms in spontaneously hypertensive rats (SHR) have yielded conflicting results, as many have used: 1) rats of only one age; 2) a single organ such as heart or brain; or 3) either Wistar-Kyoto (WKY) or an outbred normotensive control rat. We have studied the turnover of norepinephrine (NE) in three brain areas (cortex, hypothalamus, brain stem) and three peripheral organs (duodenum, skeletal muscle, kidney) of SHR, WKY, and Wistar rats at 5, 9, and 18 weeks of age. The rate of decline of norepinephrine [NE] in tissue was determined with a fluorescence assay at 0, 2, 4, and 8 hours after inhibition of tyrosine hydroxylase with alpha-methyltyrosine. Differences in NE turnover were inferred by comparing slopes of regression lines calculated for the plot of log [NE] (expressed as a percent of the initial concentration) vs time. Systolic arterial pressure of SHR was similar to that of WKY and Wistar rats at 5 weeks of age, but increased to 150 mm Hg by 9 weeks and reached an average of 190 mm Hg by 18 weeks. The turnover of NE in 5-week-old SHR compared to two normotensive strains was significantly lower in the cortex and significantly higher in the kidney and skeletal muscle. By 9 weeks, in SHR, NE turnover had increased significantly in the hypothalamus and brain stem, while decreasing significantly in the kidney and duodenum. No such changes were seen in these organs of WKY or Wistar rats when comparing turnover of NE at 5 and 9 weeks. At 18 weeks, there were no further differences in the organs of SHR when compared to values obtained at 9 weeks. These data support the hypothesis that the turnover of NE may be altered in central and peripheral organs of young SHR, and may initiate or contribute to the development of hypertension. Changes in turnover of NE in the brain and peripheral organs between 5 and 9 weeks in SHR suggest compensatory responses to increasing arterial pressure; however, similar changes in turnover were not seen between 9 and 18 weeks, although arterial pressure continued to increase.