Early potential impairment of renal sensory nerves in streptozotocin-induced diabetic rats: role of neurokinin receptors.
BACKGROUND
Electrophysiological studies in the mammalian kidney have identified two major classes of sensory receptors of the afferent renal nerves; chemoreceptors (CR) and mechanoreceptors (MR). The localization of calcitonin gene-related peptide (CGRP) and substance P (SP) in these renal pelvic sensory neurons provides an anatomical basis for a possible functional interaction between the two neuropeptides and SP receptor. The present study was performed to examine the possible changes in the responsiveness of renal sensory SP and CGRP receptors in rats with streptozotocin (STZ)-induced diabetes mellitus. Due to the crucial role of renal pelvic SP and CGRP receptors in the activation of renal sensory neurons by various stimuli, we examined whether the responsiveness of MR or CR activation and the dorsal root ganglia content of neuropeptides and neurokinin 1 receptors (NK(1)R) were altered in diabetic rats compared with non-diabetic rats.


METHODS
Afferent renal nerve activity (ARNA) was recorded from the peripheral portion of the cut end of one renal nerve branch placed on a bipolar silver wire electrode. T(13) dorsal root ganglia (DRG) immunoreactivity was performed to NK(1)R, SP and CGRP.


RESULTS
The results of the current study confirmed that the stimulation of renal MR and CR elicited a renorenal reflex response, and that the renal pelvic administration of SP and CGRP increased ipsilateral ARNA and contralateral urinary sodium excretion with no changes in arterial pressure. We also found a decrease in NK(1)R expression followed by an increase in SP and CGRP levels in the DRG of diabetic rats. The ARNA response, produced by renal pelvic MR and CR stimulation, was found to be significantly attenuated in the STZ-induced diabetic model. Conclusions. These data may indicate a compensatory synthesis and/or abnormal axonal delivery of neurokinins from the cell body to synaptic portions of the neuron as the underlying reason for attenuated ARNA in renal sensory neurons of diabetic rats.
Boer
Patrícia Aline
PA
Disciplina de Medicina Interna, Laboratório de Metabolismo Hidro-Salino, Núcleo de Medicina e Cirurgia Experimental, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 13083-970 Campinas, SP, Brazil.
Rossi
Cíntia de Lima
Cde L
Mesquita
Flávia Fernandes
FF
Gontijo
José A R
JA
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D009479:Neuropeptides / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D009479:Neuropeptides; D018377:Neurotransmitter Agents; D018040:Receptors, Neurokinin-1; D014665:Vasodilator Agents; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide