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Effects of Acute Unilateral Renal Denervation in the Rat

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Effects of Acute Unilateral Renal Denervation in the Rat Effects of acute unilateral renal denervation in the rat. E Bello-Reuss, … , R A Mueller, C W Gottschalk J Clin Invest. 1975;56(1):208-217. https://doi.org/10.1172/JCI108069. Research Article Studies were undertaken to characterize the renal responses to acute unilateral renal denervation and the mechanisms involved in these responses. Denervation was produced in anesthetized nondiuretic rats by application of phenol to the left renal artery. Studies were also performed in sham-denervated nondiuretic rats. Whole kidney and individual nephron studies were performed before and after denervation or sham denervation. Denervation increased urine volume from the left kidney to about twice its control value (P less than 0.001) and increased urinary sodium excretion from 332 neq min minus -1 to 1,887 neq min minus -1 (P less than 0.001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) remained unchanged in both kidneys after the procedure. The innervated right kidney showed no changes in urine volume or in sodium excretion. After denervation, late proximal ratio of tubular fluid inulin concentration to that of plasma [(F/P)In] decreased from 2.23 to 1.50 (P less than 0.001) while single nephron GFR remained unchanged. Absolute reabsorption decreased from 16.5 to 9.9 n. min minus -1 (P less than 0.001). (F/P)In ratios were also decreased in early distal (from 6.21 to 3.18, P less 0.001) and late distal convolutions (from 16.41 to 8.33, P less than 0.001) during the experimental period. (F/P)Na ratios remained unchanged in the early distal convolutions, but increased from 0.18 to 0.38 […] Find the latest version: https://jci.me/108069/pdf Effects of Acute Unilateral Renal Denervation in the Rat ELSA BELLO-REUSS, ROMULO E. COLINDRES, ENRIQUE PASTORIZA-MUNOZ, ROBERT A. MUELLER, and CARL W. GOTTSCHALK From the Departments of Medicine and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514 A B S T R A C T Studies were undertaken to characterize after denervation were always small. There were no the renal responses to acute unilateral renal denervation changes in GFR, RPF, urine volume, urinary sodium and the mechanisms involved in these responses. Dener- excretion, or late proximal (F/P)i. after sham dener- vation was produced in anesthetized nondiuretic rats vation. We conclude that the diuresis and natriuresis by application of phenol to the left renal artery. Studies seen after acute renal denervation were caused by a were also performed in sham-denervated nondiuretic marked depression of sodium and water reabsorption rats. Whole kidney and individual nephron studies were in the proximal tubule with partial compensation in more performed before and after denervation or sham dener- distal nephron segments. These responses appeared to vation. Denervation increased urine volume from the be unrelated to systemic or intrarenal hemodynamic left kidney to about twice its control value (P < 0.001) changes. The results demonstrate an effect of the re- and increased urinary sodium excretion from 332 neq nal nerves on proximal tubular function. min' to 1,887 neq min' (P <0.001). Glomerular fil- tration rate (GFR) and renal plasma flow (RPF) re- mained unchanged in both kidneys after the procedure. INTRODUCTION The innervated right kidney showed no changes in The influence of the renal nerves on the regulation of urine volume or in sodium excretion. After denerva- sodium and water excretion by the kidney has been a tion, late proximal ratio of tubular fluid inulin concen- subject of controversy yet to be resolved. It has long tration to that of plasma [ (F/P) In] decreased from been known that renal denervation leads to diuresis and 2.23 to 1.50 (P < 0.001) while single nephron GFR natriuresis in several mammalian species (1-6). Recent remained unchanged. Absolute reabsorption decreased studies suggest that this "denervation diuresis" is from 16.5 to 9.9 nl min' (P <0.001). (F/P) i ratios mainly the result of an effect of the renal nerves on were also decreased in early distal (from 6.21 to 3.18, tubular function (1-3). There are, however, contradic- P <0.001) and late distal convolutions (from 16.41 to tory results and it has been suggested by some (4, 5) 8.33, P < 0.001) during the experimental period. that the responses are due to an increased filtered load (F/P) Na ratios remained unchanged in the early dis- of sodium, secondary to increases in renal plasma flow tal convolutions, but increased from 0.18 to 0.38 (P < (RPF)' and glomerular filtration rate (GFR). 0.01) in late distal convolutions after denervation. Ab- The purpose of this study was to further characterize solute Na reabsorption after denervation increased in the changes in salt and water reabsorption by the kidney the loop of Henle, distal convolution, and collecting after acute unilateral denervation. We were particularly ducts. Any changes in intrarenal hydrostatic pressures interested in determining the sites of the nephron in- volved in the response and in gaining some insight into This work was presented in part at the 66th Annual the mechanisms that might explain this response. Meeting of the American Society for Clinical Investigation, Atlantic City, N. J., 5 May 1974. 'Abbreviations used in this paper: (F/P) In ratio of Dr. Bello-Reuss was an International Postdoctoral Re- tubular fluid inulin concentration to that of plasma; search Fellow of the National Institutes of Health, TW (F/P)Na. ratio of tubular fluid sodium concentration to 1998-02. Dr. Gottschalk is a Career Investigator of the that of plasma; GFR, glomerular filtration rate; PAH, American Heart Association. para-aminohippurate; RPF, renal plasma flow; SN, single Received for publication 22 January 1975. nephron. 208 The Journal of Clinical Investigation Volume 56 July 1975-208-217 Our results show that acute unilateral renal dener- higher than 90 mm Hg and, when measured, a late proxi- vation in the rat increases in urinary sodium mal tubular transit time less than 11 s were used. produced Collections of tubular fluid. In a group of 21 animals, and water excretion in the absence of changes in RPF late proximal tubular fluid collections were performed while and GFR. A marked depression of salt and water reab- simultaneously urine volume, sodium excretion, GFR, and sorption in the proximal tubule after denervation was in some instances RPF were measured. Late proximal con- partially compensated for by increased salt and water volutions were selected by injecting small amounts of in the of distal nigrosin dye into proximal convolutions with small tipped reabsorption loop Henle, convolution, pipettes (external tip diameter, 4 1Lm) and identifying the and collecting duct, so that only a small fraction of the last loops on the surface. In some animals, late proximal load which escaped reabsorption by the proximal tubule convolutions were identified with the use of a 5% buffered was excreted in the urine. solution of FD & C green dye (Keystone Aniline & Chemi- cal Co., Chicago, Ill.) .' The collections were performed with sharpened micropipettes having an external tip di- METHODS ameter of 9-12 jm. A column of stained mineral oil, 3-4 tubular diameters long, was introduced into the lumen and Observations are reported on 62 male Sprague-Dawley rats, fluid was collected at a rate such that the oil block was weighing 210-330 g. The animals were fasted overnight and maintained stationary, just distal to the pipette tip, while anesthetized with intraperitoneal sodium pentobarbital, 50 avoiding changes in tubular diameter. Tubular fluid samples mg/kg body wt. Intermittent i.v. doses of the drug were were collected from three or more convolutions for an used as needed throughout the experiment. A tracheostomy average of 2.5 min (range 1.5-3 min). The volume of fluid was performed, the animals were placed on a heated board, obtained was measured in calibrated capillary tubing and and the body temperature was maintained at 370C. Catheters its inulin concentration determined. After the control period, were placed into an external jugular vein for the infusion denervation was performed and collections were obtained of 0.9% NaCl solution at a rate of 2 ml/h, and for other from the same or from new convolutions. infusions. Arterial blood pressure was monitored from a In 11 animals, distal tubular fluid was also collected. femoral artery by means of a Statham pressure transducer After denervation, new distal tubules were always selected (Model P23 Db, Statham Instruments, Inc., Oxnard, Calif.) in these experiments. The tubules were identified as early or connected to a Beckman RP Dynograph recorder (Beck- late by the intravenous injection of FD & C green dye. man Instruments, Inc., Fullerton, Calif). The left kidney For this purpose, "early distal convolutions" were identified was exposed through an abdominal incision and prepared as those where the dye first appeared on the surface of for micropuncture as previously described (7). The peri- the kidney, after its transit through the loop of Henle. toneal reflection covering the kidney and the perirenal fat "Late distal convolutions" were identified as those where the were left intact. Both ureters were cannulated near the dye last appeared on the surface. In previous studies from kidney with PE 10 polyethylene tubing (Clay Adams, Div. our laboratory, convolutions so selected always corresponded of Becton, Dickinson & Co., Parsippany, N. J.), for urine to puncture sites within the first and second half of the collections. distal convolution, respectively, as determined by microdis- After the surgical procedure was completed, appropriate section.' Before denervation, the transit time to early distal amounts of [3H]inulin (ICN, Irvine, Calif.) or nonradio- convolutions averaged 39±2 s; after denervation it averaged active inulin2 and ["C]para-aminohippurate (PAH) (New 32±2 s (P < 0.02).
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