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Mechanism of the Antidiuretic Effect Associated with Interruption of Parasympathetic Pathways

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Mechanism of the Antidiuretic Effect Associated with Interruption of Parasympathetic Pathways Mechanism of the Antidiuretic Effect Associated with Interruption of Parasympathetic Pathways Robert W. Schrier, … , Tomas Berl, Judith A. Harbottle J Clin Invest. 1972;51(10):2613-2620. https://doi.org/10.1172/JCI107079. Research Article The present experiments were undertaken to investigate the mechanism whereby the parasympathetic nervous system may be involved in the renal regulation of solute-free water excretion. The effects of interruption of parasympathetic pathways by bilateral cervical vagotomy were examined in eight normal and seven hypophysectomized anesthetized dogs undergoing a water diuresis. In the normal animals cervical vagotomy decreased free-water clearance (C ) from H2O 2.59±0.4 se to −0.26±0.1 ml/min (P < 0.001), and urinary osmolality (Uosm) increased from 86±7 to 396±60 mOsm/kg (P < 0.001). This antidiuretic effect was not associated with changes in cardiac output, renal perfusion pressure, glomerular filtration rate, renal vascular resistance, or filtration fraction and was not affected by renal denervation. A small but significant increase in urinary sodium and potassium excretion was observed after vagotomy in these normal animals. Pharmacological blockade of parasympathetic efferent pathways with atropine, curare, or both was not associated with an alteration in either renal hemodynamics or renal diluting capacity. In contrast to the results in normal animals, cervical vagotomy was not associated with an antidiuretic effect in hypophysectomized animals. C was 2.29±0.26 ml/min H2O before and 2.41±0.3 ml/min after vagotomy, and Uosm was 88±9.5 mOsm/kg before vagotomy and 78±8.6 mOsm/kg after vagotomy in the hypophysectomized animals. Changes in systemic or renal hemodynamics or electrolyte excretion were also not observed after vagotomy in these hypophysectomized […] Find the latest version: https://jci.me/107079/pdf Mechanism of the Antidiuretic Effect Associated with Interruption of Parasympathetic Pathways ROBERT W. ScmmuER and TOMAS BERL with the technical assistance of JuDrm A. HAmuoTnii From the Department of Medicine and Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94122 A B S T R A C T The present experiments were under- systemic or renal hemodynamics or electrolyte excretion taken to investigate the mechanism whereby the para- were also not observed after vagotomy in these hypo- sympathetic nervous system may be involved in the physectomized animals. On the basis of these results, we renal regulation of solute-free water excretion. The conclude that the antidiuretic effect associated with effects of interruption of parasympathetic pathways by cervical vagotomy is initiated by interruption of para- bilateral cervical vagotomy were examined in eight sympathetic afferent pathways and is mediated by in- normal and seven hypophysectomized anesthetized dogs creased endogenous release of vasopressin. This anti- undergoing a water diuresis. In the normal animals cer- diuresis was also demonstrated to occur in the absence vical vagotomy decreased free-water clearance (CH20) of renal nerves and alterations in systemic and renal from 2.59+0.4 SE to- 0.26±0.1 ml/min (P < 0.001), hemodynamics. and urinary osmolality (U0.m) increased from 86±7 to 396+60 mOsm/kg (P < 0.001). This antidiuretic effect was not associated with changes in cardiac output, renal INTRODUCTION perfusion pressure, glomerular filtration rate, renal There is considerable evidence that the autonomic ner- vascular resistance, or filtration fraction and was not vous system, including both sympatlhetic (1-4) and affected by renal denervation. A small but significant parasympathetic pathways (5-7), is involved in the increase in urinary sodium and potassium excretion regulation of renal water excretion. The mechanisms was observed after vagotomy in these normal animals. for these effects have, however, not been entirely de- Pharmacological blockade of parasympathetic efferent fined. With the use of bioassay techniques, some in- pathways with atropine, curare, or both was not asso- vestigators have suggested that the antidiuretic effect ciated with an alteration in either renal hemodynamics of cervical vagotomy is mediated by an increase in en- or renal diluting capacity. In contrast to the results in dogenous vasopressin (ADH)' (8). Other investigators, normal animals, cervical vagotomy was not associated however, have failed to demonstrate a difference in with an antidiuretic effect in hypophysectomized ani- ADH blood levels between control and acutely hypo- mals. CH2o was 2.29±0.26 ml/min before and 2.41±0.3 physectomized animals with the use of bioassay tech- ml/min after vagotomy, and U..m was 88±9.5 mOsm/ niques (9, 10). Additional doubt as to the mechanism kg before vagotomy and 78±8.6 mOsm/kg after va- whereby cervical vagotomy may alter renal water ex- gotomy in the hypophysectomized animals. Changes in cretion is derived from the recent studies of Ledsome, Linden, and O'Connor (11) and Lydtin and Hamilton Dr. Schrier is an Established Investigator of the American (12). These investigators (11, 12) reasoned that if the Heart Association. Dr. Berl was supported by a postdoctoral fellowship from the Kidney Foundation. effect of vagotomy to abolish the diuretic effect of left This work has been presented in part at the Western Sec- atrial distension is mediated by release of endogenous tion of the American Federation for Clinical Research, ADH (5, 13), then the infusion of exogenous ADH in Carmel, Calif., February 1972, and was presented at the na- tional meeting of the American Federation for Clinical Re- 1 Abbreviations used in this paper: ADH, antidiuretic hor- search, Atlantic City, N. J., May 1972. mone; CH2O, free-water clearance; FF, filtration fraction; Received for ptblication 10 March 1972 anid in revised form GFR, glomerular filtration rate; RPF, renal plasma flow; 1 May 1972. RVR, renal vascular resistance, Uosm, urinary osmolality. The Journal of Clinical Investigation Volume 51 October 1972 2613 CONTROL__ VAGOTOMY The purpose of the present studies was to investigate Systemic Arterial _ _ _~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~further a possible role of the autonomic nervous systenm Pressure (mm Hg) 140 in the control of water excretion. Specifically, we have Renal Perfusion Pressure (mm ) 120 investigated the mechanism involved in the anticdiuretic Hg j_oo Glomerular Filtration effect of cervical vagotomy in dogs undergoing a water Rote (ml /mi n) 60 _---*-_____ diuresis. A consistent anitidiuretic effect, that was un- 60 Renal Vascular 03 -____X associate(l with alterations in systemic and relnal hemllo- Resistance dynlamics or ani increase in solute excretioln rate, was ob- (mm Hg/ml per min) l__ _ 0 served in the normal animals and this effect was not in- 300r- 11 fluence(d b\ relnal deniervationi. This antidiuretic effect of cervical vagotomy could not be duplicated by pharmaco- Urinary Osmolality t (mOsm/kg H20) 200 logical blockade of parasympathetic efferelnt p)athways. In a group of acutely hylpophysectomized aninmals undergoing 100 _ l a water diuresis, cervical vagotom) was niot associate(l with an antidiuresis. We therefore coniclu(le that the 0- antidliuretic effect associatedl with cervical vagotomy is 7 relate(d to interruptioni of parasympathetic afferent patlh- Free-Water 5 .- ways aindl inicrease(l release of endogenous vasopressin. Clearance I The p)resent results also provi(le nio support for an (ml/min ) imiiportance of altered svstem ic or renial hemo(dvunamiiics. solute excretion rate or renal innervation, or a (lirect effect of beta adrenergic stimutlationi to increase water permeability of thle tubular epithelium in the antidi- 5 0 15 50 55 60 uretic response associatedl with cervical vagotollmv. TIME (minutes) FIGURE 1 Antidiuretic effect of bilateral cervical vagotomy METHODS in the normal dog. The right kidney is denoted by the broken Experiments were performied in 19 mongrel clogs of eitlher line and the left kidney by the solid line. sex weighing 20-35 kg. Food was x-ithheld 18 hr before study, but the animals wvere allowed free access to water. On the day of study the animals wvere anesthetized with the absence of vagotomy should similarly abolish this intravenous pentobarbital (30 mg/kg), intuba.ed, and ven- diuretic effect. Both of these groups of inxvestigators tilated with a Harvard resl)irator (Harvard Apparatus Co., (11, 12), however, foulnd that the dituretic effect of left Inc., -Millis, Mass.). Liglht anesthesia was maintaine(d atrial distension was niot abolishe(d by the exogenous throughout the experimlenit by the intermittenlt administra- tion of pentobarbital. All animals received 5 mlg of deoxy- infusion of vasopressin. thius casting considerable doubt corticosterone acetate intramiiuscularly. In seven animtials on whether suppression of release of enidogenious ADH is hypophysectomy wN-as performed via a 2 cim hole in the involved in this mechanism. hard palate, through which the dura was incise(d and( the A major question thus remains as to whether the pituitary removed. These animals theni received 1 mg of with interruptioin of cer- dexamethasone intranmuscularly. In all of the animnals a antidiuretic effect associated solution of 2.5% glucose and water was then infusedl througlh vical vagal fibers is mediated through the release of a catheter in a foreleg vein at 20 ml/miinl for 50 min durinig vasopressin or through some inidependent effect on which time the following surgery was performed. Poly- neural or neurohumoral pathways. MIoreover, since cer- ethylene catheters were placed in both ureters alnd renal vical vagotomy interrupts both afferent andl efferent veins through bilateral retroperitoneal flank incisions. De- nervation of kidneys was performed by stripping and sever- parasympathetic pathways. the effect couldl be related ing the renal nerves and then applying 95% alcohol to the to interruption of parasymiipatlhetic efferent fibers rather renal pedicle. An adjustable aortic clampnwas placed aroun(l than, as proposed, the parasympathetic afferent path- the aorta above the origin of both renial arteries througl wxays. A concomitant release of increased sympathetic the left flank incision.
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