The rat renal nerves during development

Abstract

The prenatal and postnatal development of the innervation of the rat kidney has been investigated using immunocytochemical methods. The efferent innervation was studied using dopamine-beta-hydroxylase and neuropeptide Y antibodies. Calcitonin gene related peptide and substance P antibodies were used to investigate the afferent innervation. Kidneys from embryos of 14 to 20 days, from newborn rats, and from animals of 4, 10, 12, 21, 38, 60, and 90 days of age were studied. Slices of whole kidneys were analyzed, and frozen sections were used to investigate the location of the nerves in more detail. Both afferent and efferent nerves are observed inside the kidney by embryonic day 16. At birth, the afferent nerves are found (1) forming a rich plexus in the renal pelvis; (2) associated with the renal vasculature as far as the interlobular arteries (cortical radial arteries) and (3) in the corticomedullary connective tissue. The efferent innervation appears, at birth, to extend to the interlobular arteries and to the afferent arterioles of the perihilar juxtamedullary nephrons. The efferent innervation increases rapidly during the following days, and by postnatal day 21 a distribution of the innervation similar to that of the adult is observed. While the afferent innervation reaches the major target regions of the kidney by birth, the efferent does most of its expansion into the kidney postnatally. Afferent and efferent fibers are found, extrarenally and intrarenally, in the same nerve bundles. This proximity between afferent and efferent fibers may represent anatomical bases for their interaction in the adult as well as during development.

CGRP Activates Renal Pelvic Substance P Receptors by Retarding Substance P Metabolism

“…5,6,8 CGRP is known to potentiate the activation of central sensory neurons by substance P. 8 We tested the idea that CGRP may also enhance the substance P-mediated activation of renal sensory nerves. Renal pelvic administration of substance P and CGRP resulted in significant increases in ARNA when administered separately ( Figure 1).…”

“…7 We were puzzled by these findings since the CGRP-containing neurons are at least as abundant, if not more so, than the substance P-containing neurons in the renal pelvic wall. 5,6 However, there are numerous studies showing that CGRP enhances the effects of substance P at the spinal level. 8 -11,13 Therefore, we postulated that CGRP may have a similar potentiating effect on the substance P-mediated activation of renal pelvic sensory nerves.…”

“…5,6 Activation of substance P receptors in the renal pelvic area plays an essential role in the activation of renal mechanosensitive neurons. [2][3][4] The renal pelvic sensory neurons contain substance P, and increasing renal pelvic pressure increases renal pelvic release of substance P. 3,4 Similar to sensory neurons in other tissues, the renal sensory neurons also contain calcitonin gene-related peptide (CGRP), with substance P and CGRP being colocalized in many neurons.…”

“…[2][3][4] The renal pelvic sensory neurons contain substance P, and increasing renal pelvic pressure increases renal pelvic release of substance P. 3,4 Similar to sensory neurons in other tissues, the renal sensory neurons also contain calcitonin gene-related peptide (CGRP), with substance P and CGRP being colocalized in many neurons. 5,6 Administration of CGRP into the renal pelvis results in an increase in ARNA that is blocked by a CGRP receptor antagonist, suggesting the presence of CGRP receptors in the renal pelvic area. 7 However, blocking these receptors has no effect on the increase in ARNA produced by increased renal pelvic pressure.…”

“…7 This was somewhat unexpected considering that the CGRP-containing neurons appear to be more abundant than the substance P-containing neurons in the renal pelvic wall. 5,6 The present study was performed to examine the role of CGRP in the activation of renal sensory neurons. The colocalization of substance P and CGRP in many central and peripheral sensory neurons suggests a functional interaction between the 2 neuropeptides.…”