Renal sodium handling and blood pressure changes in gestational protein-restricted offspring: Role of renal nerves and ganglia neurokinin expression

• Published in: PloS one 2017-06, Vol.12 (6), p.e0179499-e0179499
• Main Authors: Custódio, Augusto H, de Lima, Marcelo C, Vaccari, Bárbara, Boer, Patrícia A, Gontijo, José A R
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Attenuation; Biology and Life Sciences; Blood; Blood pressure; Blood Pressure - physiology; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - genetics; Calcitonin Gene-Related Peptide - metabolism; Catecholamines - analysis; Clearances; Confocal; Creatinine; Creatinine - metabolism; Dams; Denervation; Diet, Protein-Restricted; Dorsal root ganglia; Excretion; Female; Functional anatomy; Ganglia; Ganglia, Spinal - metabolism; Genetic aspects; Hypertension; Immunofluorescence; Kidney - physiology; Kidney Pelvis - metabolism; Kidneys; Lasers; Lithium; Lithium - analysis; Lithium - metabolism; Low protein diet; Male; Medical research; Medicine and Health Sciences; Microscopy, Fluorescence; Nerves; Neurokinin; Neurokinin A - genetics; Neurokinin A - metabolism; Neurons; Newborn babies; Offspring; Pelvis; Physiological aspects; Potassium - analysis; Pregnancy; Pressure changes; Pressure measurement; Pressure measurements; Progeny; Proteins; Rats; Rats, Wistar; Reabsorption; Receptors; Rejection; Renal function; Sensory receptors; Social Sciences; Sodium; Sodium (Nutrient); Sodium - analysis; Sodium - metabolism; Staining; Substance P - genetics; Substance P - metabolism; Surgery
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0179499

Considering long-term changes in renal sodium handling and blood pressure in maternal protein-restricted (LP) offspring, we assumed that the development of LP hypertension results from abnormal dorsal root ganglia (DRG) neurokinin expression associated with impaired responsiveness of renal sensory receptors, promoting a reduced urinary excretion of sodium. The present study investigates whether increased blood pressure in protein-restricted offspring would be associated with changes in the DRG cells and in renal pelvic wall expression of NK1R, SP and CGRP when compared to NP offspring. In addition, we assessed the tubular sodium handling, estimated by creatinine and lithium clearances before and after bilateral renal denervation in conscious LP offspring relative to age-matched NP counterparts. Dams received a normal (NP) or low-protein diet (LP) during their entire pregnancy period. Male NP or LP offspring underwent bilateral surgical renal denervation before the 8-week renal functional test and blood pressure measurements. Immunofluorescence staining in DRG cells was assessed in optical sections by confocal laser scanning microscope. The current data demonstrated a sustained rise in blood pressure associated with a decrease in fractional excretion of sodium (FENa) by reducing post-proximal tubule sodium rejection in 16-wk old LP rats relative to age-matched NP counterparts. According to this study, bilateral renal denervation attenuated blood pressure and increased FENa in LP offspring. Furthermore, an immunohistochemical analysis showed a reduced expression of SP and CGRP in DRGs of LP when compared with NP rats. Renal pelvis of LP rats did not show a strong CGRP expression related to NP rats, whereas there was no change in SP immunostaining. These observations raise the possibility that impaired DRG and pelvic neurokinin expression associated with responsiveness of renal sensory receptors in 16-wk old LP offspring are conducive to excess renal reabsorption of sodium and development of hypertension in this programmed model.