Electrical Stimulation Of Renal Nerves Research Articles

Effect of hypotension induced by sodium nitroprusside on catecholamine overflow in the canine kidney

The overflow of noradrenaline (NA) and dopamine (DA) to plasma in the kidney in response to hypotension induced by sodium nitroprusside were studied in barbiturate-anaesthetized dogs in order to evaluate the possible existence of separately regulated renal noradrenergic and dopaminergic nerve fibres. When mean arterial blood pressure was lowered to 55 +/- 5 mmHg, arterial plasma NA, DA and adrenaline concentrations were increased and renal blood flow decreased. Renal sympathetic nerve activity was assessed by measuring the renal overflow of catecholamines to plasma. To obtain more accurate estimates of the renal contribution to catecholamines in renal venous plasma we corrected for the renal extraction of arterial catecholamines, assessed by the extraction of endogenous adrenaline. The corrected renal NA overflow to plasma increased from 164 +/- 52 to 419 +/- 137 pmol min-1 (P less than 0.05) during sodium nitroprusside induced hypotension. The renal overflow of DA to plasma was, however, not influenced significantly. The DA/NA ratio for renal venous plasma concentration as well as for renal overflow to plasma was decreased (P less than 0.05) by sodium nitroprusside induced renal nerve activation. In contrast, electrical renal nerve stimulation has previously been shown to enhance the overflows of DA and NA in parallel. One possible interpretation of these findings is that sodium nitroprusside selectively activated renal noradrenergic but not the putative dopaminergic nerve fibres while electrical stimulation activated both types of fibres.

Effect of afferent renal nerve stimulation on blood pressure, heart rate and noradrenergic activity in conscious rats

The effects of electrical stimulation of afferent renal nerves on arterial pressure, heart rate, and α-methyltyrosine-induced disappearance of norepinephrine in the hypothalamus, contralateral kidney, intestine, and skeletal muscle were studied in conscious rats. There was a significant increase in arterial pressure in response to afferent renal nerve stimulation. There was no significant change in the turnover of norepinephrine in the hypothalamus. However, there was a significant increase in the turnover of norepinephrine in the skeletal muscle, a tendency toward an increase in the intestine, and no change in the contralateral kidney. These results indicate that activation of afferent renal nerve fibers does not change noradrenergic activity in the hypothalamus yet produces a differential sympathetic outflow. Secondly, the increased turnover of norepinephrine in skeletal muscle may be contributing to

Renal overflow of noradrenaline and dopamine to plasma during hindquarter compression and thoracic inferior vena cava obstruction in the dog.

Efferent renal nerve activity was assessed by measurements of the overflow of endogenous noradrenaline (NA) and dopamine (DA) to plasma in the kidney. To obtain correct estimates of the renal contribution to the renal venous outflow of NA and DA, corrections for the renal extraction of catecholamines in arterial plasma were performed by use of tracer amounts of [3H]NA. Hindquarter compression (previously known to cause a neurogenically mediated blood pressure elevation) increased the concentrations of NA, adrenaline and DA in arterial and renal venous plasma. The renal overflow of NA increased from 83.7 +/- 32.0 to 361.3 +/- 119.4 pmol min-1 (P less than 0.05) during hindquarter compression. When compared to the renal NA overflow during electrical renal nerve stimulation, this corresponds to an increase in average renal nerve impulse activity from approximately 0.4 to 1.6 Hz. Hindquarter compression also increased the renal overflow of DA to plasma. When venous return to the heart was reduced by obstruction of the thoracic inferior vena cava, the mean arterial blood pressure fell and all catecholamines in plasma increased gradually during the first 10 min of obstruction. The renal overflow of NA was only slightly increased, indicating a minor increase in renal nerve activity. The overflow of DA to plasma was not altered by obstruction of the thoracic inferior vena cava. Neither maneuver substantially altered the DA/NA ratio for renal overflow rates or for renal venous plasma concentrations indicating that there was no preferential activation of either noradrenergic or putative dopaminergic nerve fibres.

Renal afferent input to thoracolumbar spinal neurons of the cat.

Responses of 65 thoracolumbar spinal neurons to electrical stimulation of the left renal nerves were examined in 19 cats anesthetized with alpha-chloralose. Cells were found primarily in laminae V and VII of the T12-L2 segments on the left side of the spinal cord. Renal nerve stimulation excited 55 and inhibited 10 cells. Excitatory responses were characterized either by short latency or both short and long latency responses (means +/- SE: 13 +/- 1 and 68 +/- 7 ms). Recordings of the compound action potential in the least splanchnic nerve indicated that early responses resulted from A delta-renal afferent input and long latency responses from C-fiber renal input. Maximal responses to A delta-renal input (3.3 +/- 0.5 spikes/stimulus) were significantly greater than maximal responses to C-fiber renal input (1.5 +/- 0.3 spikes/stimulus). Inhibitory responses were best demonstrated by repetitive stimuli; however, responses of five cells to single stimuli showed that these responses had long latencies to onset (36 +/- 6 ms). All cells were excited or inhibited by somatic stimuli. Excitatory somatic receptive fields invariably included the left flank region and lower abdomen, occasionally included the left hindlimb, and in a few cases included the right hindlimb. Thirteen cells had both excitatory and inhibitory somatic receptive fields. The results show that thoracolumbar spinal neurons receive renal A delta- and C-fiber input that converges with input from somatic structures. These cells may participate in renal pain which is referred to somatic structures or reflexes initiated by renal afferent fibers.

Study of prejunctional beta-adrenoceptors in kidneys of normotensive and hypertensive rats using the new beta-adrenoceptor blocking drug tertatolol.

The prejunctional beta-adrenoceptors present in the isolated perfused kidney of normotensive rats (NR) and spontaneously hypertensive rats (SHR) were compared and the effects of tertatolol on these receptors were investigated. Kidneys of NR (Wistar + Wistar-Kyoto [WKY]) and SHR, were continuously perfused with Tyrode solution at constant flow and the changes in perfusion pressure were monitored. The constrictor responses to norepinephrine (2-8 X 10(-10) moles) were slightly but significantly decreased by isoproterenol (2 X 10(-7) M) to a similar degree in NR and SHR. Tertatolol (3 X 10(-7) M) did not alter the constriction caused by norepinephrine, but abolished the dilator response to isoproterenol. Electrical stimulation of renal nerves (8 Hz) evoked constrictions in both NR and SHR; these constrictor responses were augmented in the presence of isoproterenol (2 X 10(-7) M) to a similar extent in NR and SHR. In kidneys of NR and SHR, previously incubated with 3H norepinephrine, renal nerve electrical stimulation (6 Hz) evoked an overflow of the 3H transmitter. This overflow was enhanced by isoproterenol (2 X 10(-6) M) to a similar degree in NR and SHR. Both the augmented constrictor response and the augmented overflow of 3H norepinephrine caused by electrical stimulation in the presence of isoproterenol, were inhibited by tertatolol (3 X 10(-7) M). Our results show that the beta-receptor agonist isoproterenol evokes comparable effects at prejunctional beta-adrenoceptors in kidneys of NR and SHR; they also show that tertatolol is an inhibitor of pre- and postjunctional beta-adrenoceptors in the renal circulation of the rat.

1625 RENAL NEUROADRENERGIC TRANSMISSION DURING FETAL LIFE

The renal vasoconstrictor response to graded (0.2 to 3.0 Hz, 20V, 1 msec) direct electrical renal nerve stimulation (RNS) was studied in 9 chronically catheterized fetal (F) lambs (130-142 days gestation; term 145 days) and 3 adult (A) sheep. Changes in renal blood flow (RBF) were monitored using a doppler flow-meter. During RNS, RBF (r=-0.98) decreased and renal vascular resistance (RVR) (r=0.98) increased in a dose-response relation in F and A. Following administration of phentolamine, a rise in RBF (+57% at 1.0 Hz) and a decrease in RVR (-32% at 1 Hz) were observed in F; these changes were not completely blocked with propranolol. At low frequency ( 0.4 Hz) of RNS, % changes in RBF and RVR were significantly higher in F than in A. (*for p<0.05 when F compared to A) In summary these results demonstrate that during fetal life 1) renal hemodynamics seems to be more sensitive to low frequency RNS than in A; 2) renal vasoconstriction following RNS is dependent on α adrenoceptors; and 3) renal vasodilation produced by RNS during α-blockade is not fully dependent on activation of β-adrenoceptors.

On the existence of renal vasodilator nerves.

The renal vasoconstrictor responses to graded frequencies of direct electrical renal nerve stimulation and renal arterial norepinephrine injections were evaluated before and during renal alpha-1 adrenoceptor blockade in anesthetized dogs. Renal alpha-1 adrenoceptor blockade was achieved by infusing increasing doses (1, 10, 20, 40 micrograms/kg/min) of prazosin, a selective postsynaptic alpha-1 adrenoceptor antagonist, into the renal artery. The renal vasoconstrictor response to norepinephrine (1.5 micrograms) was completely abolished by 10 micrograms/kg/min prazosin. However, the renal vasoconstrictor response to a frequency of renal nerve stimulation which produced less renal vasoconstriction than norepinephrine (1.5 micrograms) in the absence of prazosin was not abolished by either 10, 20, or 40 micrograms/kg/min prazosin. During prazosin administration, neither renal nerve stimulation nor norepinephrine produced renal vasodilatation. Therefore, at prazosin doses two- and fourfold greater than that demonstrated to produce complete renal alpha-1 adrenoceptor blockade, no renal vasodilator responses to graded renal nerve stimulation were observed. These studies provide no evidence in support of a neural renal vasodilator mechanism in the dog.

Neural control of the kidney--are there reno-renal reflexes?

Circulatory, secretory (renin release) and excretory (tubular sodium and water reabsorption) renal functions are known to be under neural control exerted by sympathetic fibers. Influences on circulatory and secretory functions are modulated by vagally mediated reflexes originated from low pressure (or volume) receptors in the cardiopulmonary area. The possibility that reno-renal reflexes may also exist has raised interest recently. Mechanoreceptors and chemoreceptors have been described in the kidney, and electrophysiological evidence of reno-renal reflexes is available. However, electrical stimulation of afferent renal nerves has failed to reflexly influence circulatory, secretory and excretory functions of the contralateral kidney. Deafferentation studies have been more successful, however. Transient denervation of one kidney by renal nerve cooling is accompanied by reduction of sodium and water excretion from the contralateral kidney with negligible changes in blood flow and glomerular filtration rate. The contralateral antidiuretic activity is prevented either by denervation of the contralateral kidney or by interruption of the afferent fibers running in the spinal dorsal roots. This definitely shows that a reno-renal reflex exists, consisting in a tonic inhibition of contralateral sympathetic activity controlling tubular reabsorption of sodium and water, and renin release.

Renal function and renal afferent and efferent nerve activity.

Recent microperfusion studies have fully substantiated the direct action of catecholamines on renal tubular reabsorptive rates. Surprisingly, these techniques have not provided consistent information on the nature of the adrenoceptor responsible for the stimulation of proximal tubular reabsorption. Both alpha- and beta-receptors have been favored for this role. These techniques have confirmed earlier reports that dopamine may have a direct natriuretic action on the renal tubules. The demonstration that renal efferent nerves contain both noradrenergic and dopaminergic fibers lends further support for the participation of dopamine in the regulation of salt and water excretion. Efferent renal nerve activity is modulated by a number of different afferent inputs to the central nervous system. One of these is the renal afferent innervation, which is composed of both chemoreceptor and mechanoreceptor fibers. A number of different reflexes that affect efferent renal nerve activity have been identified by electrical stimulation of renal afferent nerves or by selective stimulation of renal mechanoreceptors and chemoreceptors. These renorenal reflexes may have importance in the coordination of excretory activity between the two kidneys. Studies of these aspects of renal nerve function are reviewed. The importance of the renal nerves in conscious animals is also discussed in the light of evidence that their influence on renal function may be more apparent in abnormal or pathological circumstances.

A study of renal-efferent neurones and their neural connexions within cat renal ganglia using intracellular electrodes.

1. Intracellular recordings were made, in vitro, fron neurones located within left renal ganglia and left coeliac ganglia of cat solar plexus. 2. Forty-three percent of the neurones of the renal ganglia tested were identified by antidromic activation as renal-efferent neurones. 3. Electrical stimulation of all nerve trunks emanating from renal ganglia, other than the renal nerves, did not antidromically activate renal ganglia neurones. Neurones not antidromically activated were designated as non-efferent neurones. 4. Neurones within the renal ganglia were also characterized as phasic or tonic neurones depending on their pattern of discharge. 5. Electrical stimulation of renal nerves produced excitatory synaptic potentials (e.p.s.p.s) in 18% of the renal-efferent neurones. 6. Compounded e.p.s.p.s were produced in 50% of the renal ganglia neurones tested by stimulation of the ipsilateral splanchnic nerves and in 84% of the neurones upon stimulation of the vertebral nerve. 7. Synaptic responses demonstrating characteristics typical of those induced by activation of multisynaptic neural pathways were produced upon stimulation of renal and coeliac nerves. 8. The results of this study indicate that the electrophysiological properties of renal-efferent neurones vary considerably from neurone to neurone and that these neurones receive synaptic inputs from a variety of preganglionic fibres and possibly from other neurones having their soma located within the solar plexus.

Effect of renal nerve stimulation on urine and tissue kininogenase activity in cats.

The effect of electrical stimulation of efferent renal nerves on urine and renal tissue kininogenase activity was studied in cats. Handling renal nerves before crushing produced a significant increase is mean blood pressure (BP) in intact animals. After crushing, stimulation of efferent fibers (15 V, 0.5 msec, and 25 Hz) by 15-second train duration and at 2.45-minute intervals did not alter the average renal blood flow (RBF) or BP over 30 minutes. Glomerular filtration rate, water, and potassium excretion rates did not change significantly in either kidney. Sodium excretion in the ipsilateral kidney decreased significantly (p less than 0.05) in both intact and adrenalectomized cats. In intact animals, the kininogenase activity of urine (UK) also decreased significantly in both kidneys during nerve stimulation. In adrenalectomized animals it decreased significantly (p less than 0.05) only in the ipsilateral kidney, and UK of the ipsilateral kidney was significantly lower than in the contralateral (p less than 0.05). In both groups of cats, UK returned to control values during the recovery period of 30 minutes after stimulation. Adrenergic blockade abolished the effect of nerves stimulation on sodium and UK. Renal tissue kininogenase activity (RK) per gram of wet tissue was significantly lower in adrenergically blocked animals. No differences were detected when comparing RK content of ipsilateral vs a release of adrenal and peripheral nerve ending catecholamines.

Renal afferent nerves affect discharge rate of medullary and hypothalamic single units in the cat.

Abstract Electrical activity of spontaneously firing single units in the medulla and hypothalamus of 22 cats anesthetized with chloralose was monitored for changes in firing frequency during electrical stimulation of afferent renal (ARN) and carotid sinus (CSN) nerves. Stimulation of ARN altered the firing frequency of 214 out of 540 units studied in the ipsi- and contralateral medulla; the majority of the responses were excitatory but a few units (8%) were inhibited by stimulation. Of the units responding to ARN stimulation, 57% were found to respond in the same manner to stimulation of the CSN. Responsive units were found primarily in 3 regions: the lateral tegmental field, the area of the paramedian reticular nucleus and the region of the dorsal vagal complex around the obex. In the hypothalamus stimulation of ARN affected the activity of 197 of the 407 units studied ipsi- and contralaterally; the majority of the units were excited but 8% were found to be inhibited. Of the units responding to ARN 75% also responded to stimulation of the CSN. Responsive units were found in most areas but were concentrated in 3 anterior regions: lateral preoptic area, lateral hypothalamic area and the region of the paraventricular nucleus. This is the first demonstration that stimulation of afferent renal nerves can influence the electrical activity of medullary and hypothalamic neurons bilaterally. Because of the demonstrated physiological role of the structures where these responsive units were found these results suggest that sensory receptors in the kidney convey important information to central sites involved in physiological responses related to cardiovascular adjustments and fluid balance. Furthermore it has been demonstrated that the majority of medullary and hypothalamic neurons responding to stimulation of ARN also receive an input from the CSN suggesting that certain regions of both medulla and hypothalamus can integrate peripheral information from the kidney and from cardiovascular receptors to bring about appropriate homeostatic responses.

Basal norepinephrine overflow into the renal vein: effect of renal nerve stimulation.

In order to determine whether the fraction of norepinephrine released from the renal nerves that escapes into the circulation can be used an an index of renal sympathetic nervous activity, arterial and renal vein plasma norepinephrine concentrations were measured by a radioenzymatic technique along with renal blood flow in anesthetized dogs under control conditions and during electrical renal nerve stimulation. In 25 animais studied under conditions of normal sodium balance, plasma norepinephrine in the renal vein, 198 ± 26 pg/ml, was significantly higher than in arterial blood, 102 ± 10 pg/ml (P &lt; 0.001). In five dogs, electrical stimulation of the renal nerves (12 V, 3 ms) at frequencies of 0.5, 2,6, 12, and 18 Hz for 1 min was associated with increased norepinephrine concentration in renal venous plasma and an increase in the calculated renal norepinephrine overflow. There was a significant linear relationship between the frequency of stimulation and norepinephrine overflow into the renal vein in each animal, but there was also a significant interanimal variation in the slope of this relationship (P &lt;0.01). Electrical stimulation at a frequency of 2 Hz significantly decreased renal blood flow (-24 ± 7 ml/min, P &lt; 0.01). The maximal effect was achieved at 6 Hz (-66 ± 11 ml/min). The data indicate that there is a base-line overflow of norepinephrine into the renal venous blood of the dog that increases with increasing frequency of electrical nerve stimulation. They suggest that measurements of norepinephrine overflow into the renal vein may be used to assess the activity of the renal sympathetic nervous system. renal blood flow; catecholamines; renin; dog Submitted on January 10, 1980 Accepted on April 29, 1980

Hypothalamic projections of renal afferent nerves in the cat.

In 10 cats anaesthetized with chloralose the electrical activity of spontaneously active hypothalamic units was recorded for changes in discharge rate during electrical stimulation of renal afferent nerves. The discharge rate of 141 single units was altered by stimulation of either the ipsilateral or contralateral renal nerves. Most of the responsive units were located in the regions of lateral preoptic nucleus, lateral hypothalamus, and paraventricular nucleus. These results demonstrate that renal afferent nerves provide information to hypothalamic structures known to be involved in the regulation of arterial pressure and fluid balance.

Electrophysiological characteristics of renorenal reflexes in the cat.

1. Experiments were done in anaesthetized, paralysed and artificially ventilated cats to determine the fibre composition of renal nerves and to study the functional characteristics of reflex responses recorded in efferent renal nerves during electrical stimulation of contralateral and ipsilateral afferent renal nerves. 2. Renal nerves were found to contain three afferent fibre groups (Abeta, Adelta and C); the majority of these fibres reach the sympathetic chain through the least splanchnic nerve. Efferent sympathetic nerves to the kidney were found to originate from the greater, lesser and least splanchnic nerves through a synapse in the coeliac ganglion. 3. Two contralateral renorenal reflex responses were demonstrated during selective stimulation of renal afferent A and C fibres. The first (A renorenal reflex) was elicited by stimulation with trains of pulses at low voltage and high frequency (200 Hz), had an onset latency of approximately 100 msec and was followed by post-excitatory depression. The second (C renorenal reflex) was demonstrated by trains of pulses at high voltage and low frequency (20--30 Hz), had an onset latency of approximately 350 msec and was also followed by post-excitatory depression. 4. Ipsilateral renorenal reflexes with characteristics similar to the contralateral reflexes were also demonstrated. 5. Renorenal reflexes were abolished by destruction of the spinal cord and administration of nicotine sulphate (5--20 mg/kg, i.v.), but were not affected by bicuculline (0.4 mg/kg, i.f.). 6. The significance and the physiological role of these renorenal reflexes as well as their pathways within the central nervous system remain to be determined.

Humoral and mechanical factors modulating neural input to the renal vasculature.

The velocity and magnitude of neurally elicited renal vasoconstrictions decrease with reduction of renal arterial pressure. We investigated the relative roles of humoral and mechanical factors in this decrease. Cats were anesthetized with chloralose. Renal arterial pressure was controlled with an aortic cuff. Vasoconstrictions were elicited by electrical stimulation of the renal nerves until renal vascular resistance stabilized. Renal blood flow autoregulation was maintained during stimulation. Competitive blockade of angiotensin II did not affect the decrease in renal vascular responsiveness to neural input at reduced renal arterial pressure. A mathematical model suggested that a major portion of the decrease in the velocity of vasoconstrictions was a mechanical consequence of autoregulatory vasodilation. However, the model was only able to account for the experimental findings after the blockade of prostaglandin synthesis, and this blockade significantly increased the velocity of vasoconstrictions at renal arterial pressures of 75 Torr or below. These results suggested that prostaglandins as well as mechanical factors played a role in the autoregulatory decrease in responsiveness to sympathetic input.

Lack of evidence for neurogenic renal vasodilatation in anesthetized dogs.

SummaryCarotid baroreceptor reflex induced decreases in renal sympathetic nerve activity result in only minimal renal vasodilatation which is unaffected by renal cholinergic blockade with atropine.Renal cholinergic blockade with atropine does not diminish the renal vasodilation responses to decreases in renal perfusion pressure. Renal adrenergic blockade did not unmask a renal vasodilator response to direct electrical renal nerve stimulation. These findings indicate that the neurogenic contribution to renal vasodilatation is small in comparison to the neurogenic contribution to renal vasoconstriction. Evidence for participation of renal cholinergic neural pathways in renal vasodilatation was not found.

Continuous measurement of renal blood flow changes to renal nerve stimulation and intra-arterial drug administration in the rat.

A method is described for continuous measurement of renal blood flow in the anesthetized rat without dissection of the renal artery. Blood flow and arterial pressure were measured in an extracorporeal flow circuit between the carotid artery and an aortic pouch from which the left renal artery was the only outlet. Injection into the flow circuit allowed delivery of drugs directly into the arterial blood supply of the kidney. Electrical stimulation of undamaged periarterial renal kidney. Electrical stimulation of undamaged periarterial renal nerves was possible since the renal artery remained undisturbed. Extracorporeal autoperfusion of the rat kidney produced renal flow and resistance measurements that did not differ from those obtained with a flow probe placed directly on the renal artery. Renal nerve stimulation was found to cause renal vasoconstriction due to activation of alpha-adrenergic receptors by norepinephrine released from postganglionic sympathetic neurons. Renal vascular responses to a variety of intra-arterial vasoactive agents were also determined. The method described here allows the evaluation of renal vascular control in the variety of disease states for which suitable rat models have been developed.

Haemodynamic responses and renin release during stimulation of afferent renal nerves in the cat.

1. Experiments were done on anaesthetized cats to study the effect of electrical stimulation of afferent renal nerves on the circulatory system and on the release of renin from the kidney. 2. Stimulation of afferent renal nerves over a wide range of parameters consistently elicited an increase in arterial pressure and heart rate. This response was still present in paralysed animals and was not accompanied by changes in respiration or in sympathetic autonomic activity usually associated with painful stimulation. Mesenteric and iliac vasoconstriction was observed concomitantly with the increase in arterial pressure. 3. Release of renin from the contralateral innervated kidney was not significantly changed by stimulation of afferent renal nerves. 4. The existence of renal vascular mechanoreceptors was investigated by altering renal circulation. Stenosis of the renal artery or a marked reduction in renal perfusion pressure elicited an increase in arterial pressure while stenosis of the renal vein elicited a decrease in arterial pressure. These responses, however, were not affected by denervation of the kidney and were therefore interpreted as not being due to neural mechanisms. 5. The precise nature, location and physiological role of renal receptors involved in the cardiovascular responses observed during electrical stimulation of afferent renal nerves remain to be determined.