Effects of renal denervation and reinnervation on ganglionic gene expression of neurotransmitter proteins and c- fos in rat

Abstract

To investigate the molecular basis for reno-renal interactions, Northern blot analyses of sympathetic ganglia were used to study the changes in levels of mRNA encoding tyrosine hydroxylase (TH), neuropeptide Y (NPY), and c- fos at 4, 14, 21, and 56 days after denervation of the left kidney, and of c- fos mRNA at 1 and 4 h after denervation. Ganglia included in the study were right and left paravertebral chain ganglia (PVG, T 11 to L 2), celiac-mesenteric plexus (CMP), and right and left superior cervical ganglia (SCG). Levels of TH mRNA in the left PVG and CMP were decreased at 4 and 14 days compared to controls. Levels were elevated at 21 days and similar to control levels at 56 days. In the right PVG, TH mRNA levels were elevated at 4 and 14 days, diminished from this elevated level at 21 days, and similar to control levels at 56 days. No differences were found in TH mRNA levels of left or right SCG compared to controls. In long-term experiments (days), no differences in NPY or c- fos mRNA levels were found in any of the ganglia from experimental rats compared to controls. Levels of c- fos mRNA in the left PVG and CMP were decreased at 1 hour compared to control levels. By 4 h, differences in mRNA levels were no longer apparent. In the right PVG, c- fos mRNA levels were elevated at 1 hour and no longer different from control levels at 4 h. No differences were found in c- fos mRNA levels of left or right SCG compared to controls. We conclude that kidney denervation leads to acute and chronic decreases in ipsilateral ganglionic levels of c- fos and TH mRNAs, respectively, and that levels of TH mRNA return to normal only after reinnervation presumably occurs. We also conclude that unilateral denervation causes reflex increases in gene expression of c- fos and TH in the PVG innervating the contralateral kidney. Data obtained for c- fos gene expression indicate that these reflex changes have an early onset and data for TH gene expression indicate that they continue to operate until the compromised kidney is reinnervated.