Gonzalez, 1971; Mitchell, Kaufman & Iwamoto, 1983), resulting in an increased

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1 Journal of Physiology (1991), 432, pp With 2 figures Printed in Great Britain EFFECT OF SOMATIC NERVE STIMULATION ON THE KIDNEY IN INTACT, VAGOTOMIZED AND CAROTID SINUS-DENERVATED RATS BY GERARD DAVIS AND EDWARD J. JOHNS From the Department of Physiology, The Medical School, Birmingham B15 2TT (Received 6 March 1990) SUMMARY 1. The influence of cardiopulmonary and arterial baroreceptors on the renal nervedependent functional responses of the kidney to electrical stimulation of somatic afferent nerves was studied in pentobarbitone-anaesthetized rats. 2. Electrical stimulation of the left brachial nerve plexus at 3 Hz, 0-2 ms and 15 V in the intact animals increased blood pressure by 22 %, and while renal perfusion pressure was maintained at pre-stimulus levels, renal blood flow and glomerular filtration rate decreased by 14 and 22 % respectively. At the same time urine flow rate and absolute and fractional sodium excretion decreased by 36, 42 and 27 % respectively. In animals subjected to acute renal nerve section these renal functional responses could not be elicited. 3. Following bilateral vagotomy the systemic and renal haemodynamic responses to brachial nerve stimulation were similar to the intact group. However, urine flow rate and absolute and fractional sodium excretions decreased by 50, 59 and 47 % respectively, responses which were significantly greater than in the intact group. 4. In a group of rats in which the carotid sinus nerves had been sectioned, stimulation of the brachial plexus caused reductions of renal blood flow and glomerular filtration rate of the same magnitude as in the intact group; however, urine flow rate and absolute and fractional sodium excretion fell by 51, 60 and 48%, respectively, which were significantly larger than in the intact group. 5. These results demonstrate that the afferent nerve information arising from muscle joints and skin and carried via the brachial plexus caused reflex renal nervedependent reductions in renal haemodynamics and an antidiuresis and antinatriuresis. The cardiopulmonary and carotid sinus baroreceptors exert a tonic inhibitory action on these reflex renal responses insofar as they appeared to attenuate the antidiuretic and antinatriuretic responses to somatic afferent nerve stimulation. INTRODUCTION The exercise pressor reflex has both peripheral and central components (Mitchell, 1985). The peripheral limb of the reflex is initiated by activation of group IV, somatic afferent nerve fibres, arising from sensory receptors in skin, joints and muscle, which discharge into group III and IV 'somatic' afferent nerves (Coote, Hilton & Perez- Gonzalez, 1971; Mitchell, Kaufman & Iwamoto, 1983), resulting in an increased MS 8330

2 574 G. DAVIS ANDE. J. JOHNS sympathetic nerve activity, which functionally increases heart rate (Sato & Schmidt, 1987) and peripheral resistance (Thames & Abboud, 1979). With regard to the kidney, Abboud, Mark & Thames (1981) showed that brief periods of high-frequency stimulation of the somatic afferent fibres contained within the sciatic nerve induced a profound decrease in renal blood flow which was approximately frequency related. Handa & Johns (1987), using the rat, found that stimulation of the somatic sensory fibres of the brachial nerve plexus at much lower frequencies increased renal sympathetic nerve activity which was associated with only minor falls in renal haemodynamics but large decreases in the excretion of sodium. At the level of the central nervous system a number of interactions may occur. It is now clear that the pressure receptors of the cardiovascular system can influence renal sympathetic nerve activity. Karim, Kidd, Malpus & Penna (1972) demonstrated that raising left atrial pressure in the dog, by inflating a small balloon in the pulmonary vein-left atrial junction, resulted in a decreased renal sympathetic efferent nerve activity and this response was blocked by cooling or sectioning the cervical vagi (Linden, Mary & Weatherill, 1980). In functional terms, atrial stretch in the dog (Prosnitz & DiBona, 1978) and the rat (Kaufman, 1984) caused an increase in sodium excretion in the absence of any change in renal blood flow. Arterial baroreceptors also lead to changes in renal sympathetic outflow as increasing the blood pressure in isolated carotid sinuses of dog (Kidd, Linden & Scott, 1981), or cat (Coote & Downman, 1969; Ninomiya & Irisawa 1975), or using pressor drugs in the rat (Coote & Sato, 1977), resulted in a powerful inhibition of renal sympathetic nerve activity. Conversely, renal sympathetic nerve activity was increased during episodes of bilateral carotid sinus occlusion (Beers, Carroll, Young & Guyton, 1986). These reflex increases and decreases in renal nerve activity caused reciprocal changes in sodium and water excretion, with minimal alterations in renal haemodynamics (Beers et al. 1986). Together, these reports show that both the high- and low-pressure baroreceptors of the cardiovascular system can modulate sympathetic outflow to the kidneys. There is evidence from electrophysiological studies which show that afferent nerve impulses arising from somatic sensory receptors, cardiopulmonary receptors and carotid sinus baroreceptors terminate at similar sites in the central nervous system in the rabbit (Terui, Saeki & Kumada, 1987) and cat (Ciriello & Calaresu, 1977). This convergence has been observed from a functional point of view by Abboud et al. (1981) as volume expansion attenuated the renal vasoconstriction mediated by sciatic nerve stimulation. Very little else is known of the interaction between the somatic afferent input and the cardiovascular receptors in terms of the neural control of fluid handling. Therefore the primary aim of this study was to characterize the renal haemodynamic and tubular responses to activation of the afferent nerves which arise from muscle and cutaneous sensory receptors and to determine the degree to which the cardiovascular baroreceptors modify these renal responses. The approach used was to stimulate the brachial plexus in rats which had undergone either bilateral denervation of the vagi and/or the carotid sinus nerves and to compare the renal haemodynamic and functional responses with those from animals in which all cardiovascular sensory nerves were intact.

3 SOMATIC RECEPTORS AND RENAL FUNCTION 575 METHODS Male albino Sprague-Dawley rats ( g) were fasted overnight. They were anaesthetized with sodium pentobarbitone, 60 mg kg-' intraperitoneally, which was maintained by a 3 mg kg-' h-', intravenous infusion. The right brachial artery was cannulated to measure systemic arterial blood pressure (Statham P23 ID transducer to Hato Rey, Puerto Rico and Grass model 7 polygraph, Quincey, MA, USA), and to allow removal of blood samples. The femoral vein was cannulated to permit infusion of saline (150 mm-nacl) and drugs. An intravenous infusion of saline, at 6 ml h-', was begun immediately after cannulation and lasted for the duration of the experiment. An iliac artery was cannulated such that the cannula tip lay in the aorta just below the level of the left renal artery. A thread was passed around the aorta, rostral to the left renal artery, and was attached to a screw device which, by loosening or tightening enabled renal arterial pressure to be regulated at control levels. The left brachial nerve plexus was isolated from surrounding tissue and placed on bipolar stimulating electrodes. The left kidney was exposed via a mid-line abdominal incision, its ureter was cannulated and the renal artery cleared to allow fitting of an electromagnetic flow probe (Carolina EP100 series probe and FM501 flowmeter, King, NC, USA). Zero blood flow was obtained by transiently occluding the renal artery. On completion of surgery a 2 ml primer (10 mg ml-' inulin in saline) was given intravenously and the infusion changed to one containing inulin, 10 mg kg-', in saline. Measurements were begun 2 h later. Experimental protocol. This consisted of five 15 min clearance periods, two before and two following a period during which the brachial nerve plexus was stimulated. A Grass model 8 stimulator (Quincey, MA, USA) provided square-wave pulses, at 15 V, 0-2 ms duration and 3 Hz frequency, which were used to stimulate the brachial nerve plexus. At least 5 min were allowed from the beginning of stimulation before the start of the urine collection for adjustment of the renal perfusion pressure to the pre-stimulus value and for pre-formed urine to clear the dead-space of the cannula. Analyses. Arterial blood samples (0-6 ml) were collected into cooled syringes at the beginning and end of the first and last pair of clearance periods. The samples were centrifuged immediately, and the plasma removed and stored at , while the cells were resuspended in an equal volume of saline and reinfused into the animal as soon as possible. Inulin was measured as previously described (Johns, Lewis & Singer, 1976) and its clearance taken as a measure of glomerular filtration rate. Plasma and urine sodium concentration was measured by emission spectroscopy (Corning 410c). Intact group. In this group all baroreceptor afferent nerves and renal sympathetic efferent nerves remained intact. Renal denervation. During the surgical preparation, all nerves arising from the coeliac ganglion were sectioned, the renal artery was painted with absolute alcohol and the denervation was confirmed by showing that the renal blanching, which occurred in response to a 5 s period of 10 Hz electrical stimulation of the coeliac ganglion, was abolished. Vagotomy. Both vagi were sectioned in the neck region as they ran parallel with the common carotid arteries. This was carried out 1 h following the administration of the primer. Carotid sinus denervation. Using a Zeiss model 212 surgical microscope, both internal carotid arteries were stripped of all nervous and connective tissue from the carotid bifurcation to the point at which they entered the skull and were then painted with absolute alcohol. This procedure was undertaken during the main surgical preparation. The combined carotid sinus denervation and vagotomy was performed during the surgical preparation. Statistics. The average value of the two clearance periods before and the two following brachial nerve stimulation (control) was compared to that obtained during the period of stimulation (experimental). The absolute and percentage values quoted represent means + standard error of the mean. Student's paired t test was carried out on data within individual groups, the difference between means being taken to be statistically significant at the 5% level. Statistical comparisons between groups were made using a one-way analysis of variance.

4 576 TABLE 1. G. DAVIS AND E. J. JOHNS Haemodynamic and renal responses to brachial nerve stimulation in the intact rat and renally denervated animals Intact (n = 6) Denervated (n = 5) Basal Expt Recovery Basal Expt Recovery SBP (mmhg) *** *** RPP (mmhg) RBF 15-5+P ** ' P P P14 (ml min-' kg-') GFR 3' * ' ±036 (ml min-' kg-') UV (1u min-' kg-') # *** X8 83X8+14X1 10P8+156 UNaV *** ' (,umol min-' kg-') FENa (%) * 1P The protocol consisted of five clearance periods, two before (Basal), one during (Expt) and two following (Recovery) brachial nerve stimulation. Abbreviations: SBP = systemic arterial blood pressure; RPP = renal perfusion pressure; RBF = renal blood flow; GFR = glomerular filtration rate; UV= urine flow rate; UNV = absolute sodium excretion; FENa = fractional sodium excretion. The results are displayed as mean + standard error of the mean. n = number of animals. *=P<0,02; **=P<0.01; ***=P<001 RESULTS Intact group Table 1 shows the haemodynamic and renal functional responses to brachial nerve stimulation in intact rats. During brachial nerve stimulation, systemic arterial blood pressure increased in these animals by 22% (P < 0001) while renal perfusion pressure was kept at its control values by adjusting the aortic loop. Renal blood flow and glomerular filtration rate fell by 14% (P < 0-01) and 22 % (P < 002) respectively during the period of brachial nerve stimulation. At the same time there were decreases in urine flow rate, absolute sodium excretion and fractional sodium excretion of 36% (P < 0001), 42% (P < 0001) and 27% (P < 002), respectively. Renally denervated group The data presented in Table 1 show that the control values for systemic arterial blood pressure, renal blood flow and glomerular filtration rate in this group were not significantly different to those obtained in the intact group. However, these animals had a higher control urine flow rate, absolute sodium excretion and fractional sodium excretion, by 185, 164 and 198 % (P < 0001 in all cases), when compared to the intact group. Systemic arterial blood pressure increased by 17 % (P < 0001), in response to brachial nerve stimulation, which was similar to that obtained in the intact group. In this group there were no decreases in renal blood flow, glomerular filtration rate, urine flow rate, absolute sodium excretion or fractional sodium excretion in response to brachial nerve stimulation. This pattern of response was very different from that observed when the renal nerves were intact. Vagotomy group The data in Table 2 present the haemodynamic and renal functional responses to brachial nerve stimulation in rats which had undergone bilateral vagotomy. The control values for renal haemodynamic and excretory variables in the vagotomy

5 SOMATIC RECEPTORS AND RENAL FUNCTION group were comparable to those recorded in the intact group. Somatic afferent nerve stimulation, in these animals, resulted in increases in systemic arterial blood pressure of 24 % (P < 0-001) and while the renal perfusion pressure was successfully regulated during the experimental period, glomerular filtration rate decreased by 25 % 0) 40 - Intact VX CSX VX-CSX Xus 20 iii 0 0) L C c=-201 L] w t 0 ~'-20 =40] Fig. 1. Percentage changes in systemic and renal haemodynamic variables in response to brachial nerve stimulation in intact, vagotomized (VX), carotid sinus-denervated (CSX) and vagotomized plus carotid sinus-denervated (VX-CSX) rats. SBP = systemic blood pressure, RBF = renal blood flow, GFR = glomerular filtration rate. (P < 001). All the haemodynamic responses were similar in magnitude to those recorded in the intact group. Figure 1 shows a comparison of the percentage changes in renal haemodynamic variables obtained during brachial nerve stimulation between the intact group and the vagotomized group. Urine flow rate, absolute sodium excretion and fractional sodium excretion decreased during brachial nerve stimulation by 50, 59 and 47 % respectively (P < in all cases), responses which were greater than those recorded in the intact group by 50, 59 and 127 % (P < 0 03 in all cases). A comparison of the percentage changes in the excretory variables is shown in Fig. 2. Carotid sinus-denervated group The data displayed in Table 2 illustrate the haemodynamic and renal functional responses of brachial nerve stimulation in rats which had undergone bilateral carotid sinus denervation. Immediately following the denervation blood pressure increased in four of the six rats from to mmhg (P < 0 01) but in the subsequent two hours gradually decreased to the basal values quoted in Table 2. The basal values 19 PHY 432

6 578 G. DAVIS AND E. J. JOHNS for systemic arterial blood pressure in the bilateral carotid sinus-denervated group were lower, by 18 % (P < 0 02), compared to the intact group, while renal blood flow and glomerular filtration rate, urine flow rate, and absolute and fractional sodium excretion were similar in the two groups. 0 Intact VX CSX VX-CSX 0) ī C.) ' 0 - ad m o X -30 -i Fig. 2. Percentage changes in renal functional variables in response to brachial nerve stimulation in intact, vagotomized (VX), carotid sinus-denervated (CSX) and vagotomized plus carotid sinus-denervated (VX-CSX) rats. UV= urine flow rate, UNAV = absolute sodium excretion, FENa = fractional sodium excretion. Electrical stimulation of the brachial plexus in the carotid sinus-denervated group increased systemic arterial blood pressure by 31 % (P < 0 001) and was accompanied by reductions in renal blood flow of 14 % (P < 0 02) and glomerular filtration rate of 26 % (P < 0-0 1). These haemodynamic responses were similar to those obtained during the experimental period in the intact group and a comparison of the responses is shown in Fig. 1. Brachial nerve stimulation in these carotid-sinus-denervated animals resulted in a reduction in urine flow rate of 51 % (P < 0-001), in absolute sodium excretion of 60% (P < 0-001), and in fractional sodium excretion of 48% (P < 0 01), and all these responses were significantly larger than those recorded in the intact group (P < 0-01 in all cases). The percentage changes of these variables are shown in Fig. 2.

7 SOMATIC RECEPTORS AND RENAL FUNCTION 579 > ; _ X o ce m*>* C)o Cz o ce 4-' 0 c * O1+1 c+ Ca -t LC ce, c 4* o * c^ t OONO e ; > X ~+l +l +l +l +l +l +l C3 stl < n: N C e 7 X Z O0 4.D Qe cd o~~~~~~~~~~~ l+l+l> e=r * ~~*** 11 _~ ~ Et = u- C1 N ii ce 4-~ ~ ~ ~O V*-Xe > t = m X m X o X Xo~~~~~~~c tf aq~~~~~~~~~~~~~~~~c cde t- C 0 0e c S ; 11 ce > ~~+l +l +l +l +l +l +l * ee 11+^5 = -1. cq r~~~~~~~~~~~~~~~~~~~~; ce - C) n neoo t _ e < _ Ca 1) X Q t ~~c e ~ ~ ce. c0_ r ~ -~~~ r~~~- A O 5,; il~~~~c -: ~ =;10:.4- :sec EQ~~~~~~~~~~~~~~~~14-11 ;4 E Z $ z L L W L X 19-2

8 580 G. DA VIS AND E. J. JOHNS Vagotomy plus carotid sinus denervation The data in Table 2 show the haemodynamic and renal functional responses to brachial nerve stimulation in animals which had undergone both vagotomy and carotid sinus denervation. Control levels of systemic arterial blood pressure were similar to those measured in the intact animals; however, renal blood flow and glomerular filtration rate were lower by 33 and 30% (P < in both cases). Control values for urine flow rate, absolute sodium excretion and fractional sodium excretion were lower than those obtained in the intact group by between one-third and two-thirds (P < 0-02 in all cases). Brachial nerve stimulation, in these animals resulted in a 35 % (P < 0 01) increase in systemic arterial blood pressure, a response which was not different from that measured in the intact group. During this period renal perfusion pressure was regulated at an unchanged level and while renal blood flow did not change, glomerular filtration rate decreased by 55 % (P < 0-02). A comparison of the percentage changes in renal haemodynamics is illustrated in Fig. 1. Brachial nerve stimulation did not change fractional sodium excretion, but decreased urine flow rate by 79 % (P < 0 001) and absolute sodium excretion by 69 % (P < 0-01). The magnitudes of these latter responses were shown to be similar in absolute terms to the responses obtained in the intact animals, but because of the lower control levels they were proportionately larger. A comparison of the percentage changes in these excretory variables is shown in Fig. 2. DISCUSSION In this study the brachial plexus was electrically stimulated at 3 Hz, 0-2 ms duration and 15 V which were parameters chosen to ensure depolarization of group IV muscle and cutaneous afferent nerves (Coote & Perez-Gonzalez, 1970) and it was most likely that stimulation of these afferent nerves was responsible for the increased blood pressure when the brachial nerve plexus was stimulated. This somatic afferent activation gave rise to a small renal vasoconstriction, a decrease in glomerular filtration rate and a concomitant antidiuresis and antinatriuresis, all of which were abolished in the renally denervated animals demonstrating that these responses were primarily mediated by actions of the renal nerves. These functional findings were similar to those reported previously in renally denervated rats (Handa & Johns, 1988). Indeed, in an earlier study we showed that such electrical stimulation of the somatic afferent nerves caused a 20 % increase in recorded nerve activity (Handa & Johns, 1987) which was similar to the responses observed in preliminary experiments on four rats undertaken for this report. The renal nerve-dependent decrease in sodium output may result from two causes; firstly the renal vasoconstriction and the reduction in filtered load, due to the fall in glomerular filtration rate, would themselves decrease the rate of sodium excretion; secondly, the renal nerves have a direct action on tubular cells to stimulate sodium reabsorption (DiBona, 1982). The relative contribution of these two neurally induced effects to the overall renal excretory response is difficult to assess. However, Hesse & Johns (1984) demonstrated in the rabbit that falls in renal blood flow of up to 15 %

9 SOMATIC RECEPTORS AND RENAL FUNCTION contributed minimally to the observed antinatriuresis and antidiuresis resulting from direct renal nerve stimulation. It was therefore likely that in the present study the major component of the nerve-mediated antinatriuresis and antidiuresis was caused by the direct tubular action of the nerves. In the present study, bilateral cervical vagotomy would have abolished afferent information from not only the cardiopulmonary region, but also the gut and other visceral organs. In addition, the aortic arch baroreceptor nerve fibres, which are closely applied to the vagus, were also sectioned. The question arises as to which of these groups of afferent nerves are responsible for the attenuation of the somatic reflex. Mechanical stretch of the atria in the dog (Kidd, Ledsome & Linden, 1978) led to a renal nerve-dependent diuresis suggesting atrial activation could have an important impact on the kidney. It has also been demonstrated that thoracic vagotomy did not abolish the diuresis induced by atrial distension (Mancia, Donald & Shepherd, 1973). Further it has been shown that renal sympathetic activity is influenced to a greater extent by atrial baroreceptors than visceral receptors (Weaver, Genovesi, Stella & Zanchetti, 1987). Together this evidence would support the suggestion that in the present study the increased magnitude of the renal excretory responses to somatic nerve activation was due to removal of information originating in the atria. The control levels of renal haemodynamic and functional variables in the bilaterally vagotomized animals were similar to those obtained in the intact animals. During brachial nerve stimulation in this vagotomized group, the haemodynamic changes were similar to those elicited in the intact group of animals. By contrast there were large antidiuretic and antinatriuretic responses which were significantly greater than those obtained in the intact group. These findings would be consistent with the view that under normal conditions activation of somatic nerves would lead to increased renal sympathetic outflow and consequent functional responses, the magnitudes of which were tonically inhibited by information carried in the cervical vagus nerves. This important finding supports the reports of Thames & Abboud (1979) who showed in dogs that progressive volume expansion resulted in a decrease in the renal vasoconstriction resulting from somatic afferent nerve stimulation. Conversely, in humans, unloading the cardiopulmonary baroreceptors, by applying lower body negative pressure, greatly increased forearm vasoconstriction during isometric exercise (Walker, Abboud, Mark & Thames, 1980). Both of these experiments implicate an important regulatory role for the cardiopulmonary baroreceptors in the sympathetic nerve response to exercise. The observations of the present investigations show that this role of the cardiopulmonary baroreceptors extends to the modulation of the functional response of the kidney. The lower systemic arterial blood pressure in the group of rats subjected to bilateral carotid sinus denervation was unexpected. It was evident that the immediate response to the bilateral carotid sinus denervation was an elevation of blood pressure which amounted to some 18+3 mmhg in four of the six rats and represented a classical response to removal of carotid sinus output. However, this elevation of blood pressure was not sustained and during the 2 h equilibrium period it drifted to a level somewhat lower than that observed in intact animals. One possible reason for the lower blood pressure could have been the decreased 581

10 G. DAVIS AND E. J. JOHNS chemoreceptor activity, as during the surgical procedures to section the sinus nerves it was almost certain that the afferent nerves arising from the carotid bodies were removed. These nerves provide an excitatory influence on sympathetic outflow. Thus, Mancia (1975) demonstrated that stimulation of the carotid body chemoreceptors was capable of increasing peripheral vascular resistance, while Marshall (1987) suggested that approximately 10% of the peripheral resistance in the anaesthetized rats was due to chemoreceptor activation. Ablation of the carotid baroreceptors resulted in control levels of renal haemodynamics or tubular function which were similar to those obtained in the intact animals. This may be due to a low tonic influence of the baroreceptors on sympathetic outflow to the kidney in this anaesthetized preparation. Alternatively, it was possible that removal of input from one group of high-pressure baroreceptors was compensated for by the remaining cardiovascular baroreceptors carried in the vagus (Thames & Ballon, 1984). This idea was supported by the observation that the increase in blood pressure during brachial nerve stimulation in this group was similar to that obtained in the intact group. However, the magnitude of the renal nervemediated antinatriuresis and antidiuresis during brachial nerve stimulation after baroreceptor denervation was significantly greater than that obtained in the intact animals. These findings indicated that the carotid sinus baroreceptors were normally exerting an attenuating influence on the somatic afferent nerve-mediated reabsorption of sodium and water. Following denervation of the cardiopulmonary and arterial baroreceptors the blood pressure and renal blood flow were no different from control animals. Glomerular filtration rate and renal functional measurements were significantly lower than those obtained in the intact group, possibly as a result of an increase in renal sympathetic nerve activity. However, it has been reported that this type of cardiovascular denervation results in an increase in plasma renin (Yun, Delea, Bartter & Kelly, 1976) and vasopressin concentration (Courneya, Rankin, Wilson & Ledsome, 1988). This combination of hormones would promote the reabsorption of sodium and water and increase vascular tone. Brachial nerve stimulation in this group of animals caused an exaggerated fall in glomerular filtration rate from its already low level which could be taken as indicating a major increase in renal sympathetic outflow. Similarly, the antinatriuretic and antidiuretic responses were greater; in proportionate terms, but this was probably due to the large reduction in filtration rate as well as a direct effect of the nerves on sodium reabsorption. It was clear that renal function was seriously disturbed following sino-aortic and vagal deafferentation and so altered control levels that comparative changes could not be undertaken. Nevertheless it is clear that stimulation of the somatic afferents could still have a major impact on the kidney. This series of experiments have demonstrated that stimulation of somatic afferent nerves resulted in relatively small changes in renal blood flow and glomerular filtration rate but in major reductions in tubular sodium and water excretion which were dependent on intact renal nerves. Removal of either the vagi or the carotid sinus baroreceptors and chemoreceptors had small effects on the magnitude of the brachial nerve stimulation. blood pressure and renal haemodynamic responses to However, these denervations resulted in an augmented antinatriuresis and

11 SOMATIC RECEPTORS AND RENAL FUTNCTION 583 antidiuresis during brachial nerve stimulation. Together, these observations suggested that there was convergence of afferent information from systemic baroreceptors and somatic sensory receptors at the central nervous system, such that there was an interaction to tonically inhibit sympathetic outflow to the kidney when the somatic afferents were stimulated. In this way the regulation of fluid retention by the kidney is protected during normal physical activity. The support of the National Kidney Research Fund and the British Heart Foundation is gratefully acknowledged. REFERENCES ABBOUD, F. M., MARK, A. L. & THAMES, M. D. (1981). Modulation of the somatic reflex by carotid baroreceptor and cardiopulmonary afferents in animals and humans. Circulation Research 48, BEERS, E. T., CARROLL, R. G., YOUNG, D. B. & GUYTON, A. C. (1986). Effects of graded changes in reflex renal nerve activity on renal function. American Journal of Physiology 250, F CIRIELLO, J. & CALARESU, F. R. (1977). Lateral reticular nucleus: a site of somatic and cardiovascular integration in the cat. American Journal of Physiology 233, R COOTE, J. H. & DOWNMAN, C. B. B. (1969). Supraspinal control of reflex activity in renal nerves. Journal of Physiology 202, COOTE, J. H., HILTON, S. M. & PEREZ-GONZALEZ, J. F. (1971). The reflex nature of the pressor response to muscular exercise. Journal of Physiology 215, COOTE, J. H. & PEREZ-GONZALEZ, J. (1970). The response of some sympathetic neurones to volleys in afferent nerves. Journal of Physiology 208, COOTE, J. H. & SATO, Y. (1977). Reflex regulation of sympathetic nerve activity in the SHR. Circulation Research 40, COURNEYA, C. A., RANKIN, A. J., WILSON, N. & LEDSOME, J. R. (1988). Carotid sinus pressure and plasma vasopressin in anaesthetised rabbit. American Journal of Physiology 255, H DIBONA, G. F. (1982). The function of the renal nerves. Reviews of Physiology, Biochemistry and Pharmacology 94, HANDA, R. K. & JOHNS, E. J. (1987). The role of angiotensin II in the renal responses to somatic nerve stimulation in the rat. Journal of Physiology 393, HANDA, R. K. & JOHNS, E. J. (1988). A study of the renal responses in the rat to electrical stimulation of the afferent nerves of the brachial plexus. Quarterly Journal of Experimental Physiology 73, HESSE, I. F. A. & JOHNS, E. J. (1984). The effect of graded renal nerve stimulation on renal function in the anaesthetised rabbit. Comparative Biochemistry and Physiology 79A, JOHNS, E. J., LEwIs, B. A. & SINGER, B. (1976). The sodium retaining effect of renal nerve activity in the cat: role of angiotensin formation. Clinical Science and Molecular Medicine 51, KARIM, F., KIDD, C., MALPUS, C. M. & PENNA, P. E. (1972). The effect of stimulation of the left atrial receptors on sympathetic efferent nerve activity. Journal of Physiology 227, KAUFMAN, S. (1984). Role of right atrial receptors in the control of drinking in the rat. Journal of Physiology 349, KIDD, C., LEDSOME, J. R. & LINDEN, R. J. (1978). The effect of distension of the pulmonary vein-atrial junction on activity of left atrial receptors. Journal of Physiology 285, KIDD, C., LINDEN, R. J. & SCOTT, E. M. (1981). Reflex responses of single renal sympathetic fibres to stimulation of atrial receptors and carotid baro- and chemo-receptors. Quarterly Journal of Experimental Physiology 66, LINDEN, R. J., MARY, D. A. S. G. & WEATHERILL, D. (1980). The nature of the atrial receptors responsible for a reflex decrease in activity in renal nerves in the dog. Journal of Physiology 300, MANCIA, G. (1975). Influence of carotid body baroreceptors on vascular resistance to chemoreceptor stimulation in the dog. Circulation Research 35,

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