title: Renal sensory and sympathetic nerves reinnervate the kidney in a similar time-dependent fashion after renal denervation in rats.
abstract: Efferent renal sympathetic nerves reinnervate the kidney after renal denervation in animals and humans. Therefore, the long-term reduction in arterial pressure following renal denervation in drug-resistant hypertensive patients has been attributed to lack of afferent renal sensory reinnervation. However, afferent sensory reinnervation of any organ, including the kidney, is an understudied question. Therefore, we analyzed the time course of sympathetic and sensory reinnervation at multiple time points (1, 4, and 5 days and 1, 2, 3, 4, 6, 9, and 12 wk) after renal denervation in normal Sprague-Dawley rats. Sympathetic and sensory innervation in the innervated and contralateral denervated kidney was determined as optical density (ImageJ) of the sympathetic and sensory nerves identified by immunohistochemistry using antibodies against markers for sympathetic nerves [neuropeptide Y (NPY) and tyrosine hydroxylase (TH)] and sensory nerves [substance P and calcitonin gene-related peptide (CGRP)]. In denervated kidneys, the optical density of NPY-immunoreactive (ir) fibers in the renal cortex and substance P-ir fibers in the pelvic wall was 6, 39, and 100% and 8, 47, and 100%, respectively, of that in the contralateral innervated kidney at 4 days, 4 wk, and 12 wk after denervation. Linear regression analysis of the optical density of the ratio of the denervated/innervated kidney versus time yielded similar intercept and slope values for NPY-ir, TH-ir, substance P-ir, and CGRP-ir fibers (all R(2) > 0.76). In conclusion, in normotensive rats, reinnervation of the renal sensory nerves occurs over the same time course as reinnervation of the renal sympathetic nerves, both being complete at 9 to 12 wk following renal denervation.
authors: Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden.
authors: Jan
authors: J
authors: Mulder
authors: Tomas
authors: T
authors: Hökfelt
authors: Mark M
authors: MM
authors: Knuepfer
authors: Ulla C
authors: UC
authors: Kopp
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003714:Denervation; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007668:Kidney / Q000294:innervation*; D007682:Kidney Pelvis / Q000294:innervation / Q000502:physiology; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D011984:Sensory Receptor Cells / Q000502:physiology*; D013373:Substance P / Q000378:metabolism; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D009478:Neuropeptide Y; D013373:Substance P; D014446:Tyrosine 3-Monooxygenase; D015740:Calcitonin Gene-Related Peptide