Objective: To investigate the effect of renal denervation on renin mRNA levels in fetal and nonpregnant adult ovine renocortical tissue and in isolated juxtaglomerular cells under basal conditions and after stimulation.
Methods: The left kidney was denervated and the right kidney subjected to a sham procedure in nine ovine fetuses (136-141 days' gestation) and 20 nonpregnant ewes. After 5-7 days the denervated and intact kidneys were obtained, and renin-containing renal cortical cells were isolated and cultured overnight. Then cells were treated with isoproterenol, forskolin, or isomethylbutyl xanthine (IBMX) for 4 hours. Total RNA was isolated and renin mRNA measured by RNase protection assay. Cyclic adenosine monophosphate (cAMP) levels were measured in the incubation medium with a competitive enzyme immunoassay.
Results: In adults, basal renin mRNA levels were significantly lower in denervated than in sham-operated kidneys. No difference was noted between denervated and intact fetal kidneys. Renin mRNA levels were significantly higher in fetal than in adult kidney tissue, and cells from fetuses had greater increases in renin mRNA after stimulation than did cells from adults. Fetal cells also released more cAMP into the incubation medium, and there was a correlation between cAMP and renin mRNA levels.
Conclusions: The data indicate the effects of renal denervation on renin mRNA expression in the kidney are age dependent and that the fetus in late gestation has a mechanism for maintaining renin mRNA levels after denervation, which is absent or nonfunctional in the adult.