DIFFERENTIAL REGULATION OF INTERLEUKIN-6 PRODUCTION IN THE KIDNEY BY THE RENAL SYMPATHETIC-NERVES IN NORMAL AND SPONTANEOUSLY HYPERTENSIVE RATS

Objective: The aim of the study was to evaluate the influence of renal sympathetic nerves on the production of interleukin (IL)-6 in the kidney of normotensive Wistar rats and spontaneously hypertensive rats (SHR). Design: In acute studies, the left kidney was exposed and the renal nerves were electrically stimulated to decrease renal blood flow by either 15 or 30% for 1 h. The changes in renal function induced by nerve stimulation were measured and IL-6 production estimated at the end of the experiment. Method: Pentobarbitone anaesthetized rats were prepared for the measurement of renal blood flow, glomerular filtration rate and water and sodium excretion. IL-6 production was estimated by the level of IL-6 messenger (m)RNA present in the kidney tissue. Results: At the lower level of nerve stimulation there were reductions in the glomerular filtration rate of 12 and 24% in Wistar and SHR, respectively, and a decrease in sodium excretion of approximately 30% in both rat strains. At higher rates of stimulation these haemodynamic and tubular responses were proportionately larger. The mRNA for IL-6 and beta-actin were measured by densitometric analysis of Northern blot gels following hybridization. Renal IL-6 mRNA levels in the Wistar rat demonstrated that the gene was actively expressed and was increased some threefold by renal nerve stimulation. By contrast, IL-6 mRNA was extremely low in SHR compared with that found in the kidneys of Wistar rats and did not appear to be changed by renal nerve stimulation. Conclusions: These findings suggest that the renal sympathetic nerves are an important regulatory mechanism for IL-6 production under normal conditions. However, in the SHR, production of IL-6 in the kidney appears to be suppressed.