Age-related changes in calcitonin gene-related peptide and substance P in renal afferent nerve soma in the rat. Association with afferent renal nerve activity.

Renal afferent neurons were retrogradely labeled with FluoroGold in Sprague-Dawley rats at 50, 60, 70, 80, 90, 110, 130 and 200 days of age. Recordings of afferent renal nerve activity (ARNA) and immunofluorescent assessment of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) and substance P (SP)-LI in spinal ganglia T10-L1 were obtained in the same rats. The frequency of renal afferent neurons positive for CGRP-LI declined abruptly from 88% in animals younger than 100 days of age (342 of 388 total cells) to 63% in rats older than 100 days of age (223 of the 353 total cells). The intensity of CGRP-LI (scaled 1-3) in renal afferent CGRP-positive neurons also declined significantly from a mean of 2.23 +/- 0.04 before 100 days to 1.48 +/- 0.05 in older rats (P < 0.001 in each age group). SP-LI positive neurons declined from 44% to 28% (P < 0.001). These changes in neuropeptide immunofluorescence coincided with an altered pattern of ARNA in which the excitatory response to complete renal ischemia increased from 274 +/- 69% above background to 1167 +/- 124% after the age of 100 days. Previous studies have shown that this alteration in the ARNA response to renal ischemia is due to the appearance of activity from R1 chemoreceptor nerves in ARNA. These data demonstrated that this transition in the electrophysiologic characteristics of ARNA is accompanied by profound alterations in CGRP-LI and SP-LI levels in renal afferent nerve cell bodies.