Quantification and classification of potassium and calcium disorders with the electrocardiogram: What do clinical studies, modeling, and reconstruction tell us?

Diseases caused by alterations of ionic concentrations are frequently observed challenges and play an important role in clinical practice. The clinically established method for the diagnosis of electrolyte concentration imbalance is blood tests. A rapid and non-invasive point-of-care method is yet needed. The electrocardiogram (ECG) could meet this need and becomes an established diagnostic tool allowing home monitoring of the electrolyte concentration also by wearable devices. In this review, we present the current state of potassium and calcium concentration monitoring using the ECG and summarize results from previous work. Selected clinical studies are presented, supporting or questioning the use of the ECG for the monitoring of electrolyte concentration imbalances. Differences in the findings from automatic monitoring studies are discussed, and current studies utilizing machine learning are presented demonstrating the potential of the deep learning approach. Furthermore, we demonstrate the potential of computational modeling approaches to gain insight into the mechanisms of relevant clinical findings and as a tool to obtain synthetic data for methodical improvements in monitoring approaches.

Atrial fibrillation in end stage renal disease patients: influence of hemodialysis on P wave duration and atrial dimension.

BACKGROUND: Prevalence and incidence of atrial fibrillation (AF) are high in hemodialysis (HD) patients. Intra-atrial conduction velocity slowing plays an important role in AF onset. The aim of our study was to measure P wave duration (Pwd), expression of intra-atrial conduction velocity, in HD patients with and without a history of AF. METHODS: The study was performed in 47 end stage renal disease (ESRD) patients, subdivided into four groups: 19 patients within the first 6 months from starting HD therapy (HD1); the same patients studied 18 ± 3 months later (HD2); patients with no history of AF and long dialytic age (HD3, n = 13); and patients with sinus rhythm but history of AF (HDAF, n = 15); and 18 healthy controls. In all patients P wave high resolution recording and electrolyte plasma values were obtained before and after a HD session, and atrial diameter was assessed by echocardiography. RESULTS: Patients with the shortest dialysis vintage showed the shortest Pwd [131.2 ± 11.0 (HD1) vs. 139.8 ± 11.7 (HD2), 142.1 ± 7.2 (HD3), 152.3 ± 15.0 (HDAF) ms; p < 0.05], while Pwd was prolonged in patients with AF history when compared to all other groups (p < 0.03). At multivariate analysis atrial dimension was independently related to Pwd (R = 0.40, p < 0.02). HD session induced a significant increase of Pwd (141 ± 14.0-152 ± 17.0 ms, p < 0.001), that was correlated to modifications of K(+) concentration (R = 0.8, p < 0.0001). CONCLUSIONS: HD therapy prolongs Pwd. HD patients with a history of AF have prolonged Pwd compared to patients without, suggesting that increased Pwd is a marker of AF risk in patients with ESRD. HD session acutely increases Pwd, creating conditions favoring AF onset.

Polymethylmethacrylate membrane and serum free light chain removal: enhancing adsorption properties.

INTRODUCTION: Polymethylmethacrylate (PMMA) membranes can adsorb a wide variety of uremic toxins including serum free light chains (sFLC). However, limited data are available regarding the clinical use of PMMA in multiple myeloma patients and its maximum adsorption capacity in this setting. AIM: This study aimed to measure the capacity of PMMA to adsorb sFLC and identify strategies to improve its efficiency in clinical practice. METHODS: Ten patients with dialysis-dependent renal failure and high levels of sFLC were included in the study. Five patients received standard PMMA hemodialysis (HD; n = 18), while in the other 5 patients a new technique called enhanced adsorption dialysis (EAD) was used, which involves PMMA dialyzer replacement after 2 h (n = 19). In all patients, sFLC were measured at the beginning and at the end of each dialysis session to calculate the difference between start and end of treatment and the percentage removal. RESULTS: PMMA membranes reduced sFLC in both the PMMA HD and EAD groups. PMMA HD showed similar efficiency on κ and λ percentage removal (22.3 and 21.0%, respectively, n.s.) but, in contrast, had a significantly greater effect on the delta of sFLC in κ [1,555 mg/l (-511 to +6,027)] versus λ [390 mg/l (120-650)] treatments (p = 0.007). EAD treatments only partially increased percentage removal of κ sFLC (22.3-31.0%, p = 0.38), while they had a significantly great effect on λ (21.0-53.1%, p = 0.003). A positive linear correlation was found between delta sFLC and pre-HD sFLC concentrations in PMMA HD κ treatments (r = 0.68, p < 0.02) but not for λ treatments (r = 0.54, p = 0.21), while the analysis of patients receiving EAD demonstrated a strong positive correlation for both κ and λ subtypes (r = 0.81 and r = 0.85, respectively, p < 0.008). In EAD sessions, a positive linear correlation was shown between blood flow during treatment and percentage removal of sFLC (r = 0.58, p = 0.02); however, with PMMA HD such a correlation was not observed (r = 0.28, p = 0.25). CONCLUSIONS: PMMA membranes can efficiently adsorb sFLC, but the process is limited by membrane saturation and is different between κ and λ sFLC. The new EAD technique can greatly improve λ removal but only partially act on κ sFLC. Therefore, EAD should be considered a valid economic treatment option without side effects in particular subsets of patients for the removal of sFLC.

Effects of adenosine receptor agonists on efferent renal nerve activity in anesthetized rats.

The aim of this study was to investigate the effects of A1 and A2 adenosine-receptor activation on the sympathetic nervous system. The effects on efferent renal nerve activity of selective A1 (CCPA; 2-chloro-N-6-cyclopentyladenosine) and A2 (2HE-NECA; 2-hexynyl-5'-N-ethylcarboxamidoadenosine) adenosine-receptor agonists were studied in anesthetized rats either with intact baroreflexes (intact rats) or with bilateral sinoaortic denervation and vagotomy (denervated rats). After a control period of 5 min, A1 or A2 agonist or vehicle were intravenously infused for 8 min in separate groups of intact or denervated rats, in which arterial pressure and heart rate were continuously recorded. CCPA (5.0 microg/kg/min) and 2HE-NECA (0.7 microg/kg/min) were selected to obtain comparable blood pressure changes over the period of observation. Arterial pressure significantly and equally decreased during the A1 (-41 +/- 8%), and A2 (-35 +/- 5%) agonist administration. Heart rate significantly decreased during A1 agonist infusion, but it did not change during A2 agonist administration. Bilateral sinoaortic denervation and vagotomy did not modify the hemodynamic responses to both drugs. The A1 and A2 administration caused a large and significant increase in efferent renal nerve activity (+66 +/- 22% and +76 +/- 15%, respectively), and this effect was entirely abolished in denervated rats. A linear relation with a significant negative slope between changes in arterial pressure and changes in neural discharge was observed for each treatment. The comparison of the regression slopes showed that the reflex increase of efferent sympathetic activity caused by the administration of both agonists was significantly smaller than the increment induced by equipotent hypotensive dose of sodium nitroprusside (10 microg/kg). These data show that the selective activation of A1 and A2 receptors elicits a reflex increase in efferent renal nerve activity. This neural activation is smaller as compared with the effect of equihypotensive doses of sodium nitroprusside, thus indicating a blunting effect of both adenosine agonists on baroreceptor sensitivity.

Role of the renal nerves and angiotensin II in the renal function curve.

The relationship between renal perfusion pressure and urinary sodium is involved in arterial pressure regulation. The aim of this study was to investigate the role of renal nerves and angiotensin II in the pressure-natriuresis relationship. Experiments were performed in anaesthetised cats in which one kidney was surgically denervated. Renal perfusion pressure (RPP), renal blood flow (RBF) glomerular filtration rate (GFR, creatinine clearance), urinary volume (V) and sodium excretion (Una + V) were separately measured from both kidneys. RPP was progressively reduced in two consecutive steps by a suprarenal aortic snare. Two groups of animals were studied: the first without any pharmacological treatment (Untreated), the second during treatment with an angiotensin converting enzyme inhibitor (Captopril, 0.4 mg/Kg intravenously followed by an infusion of 0.4 mg/Kg/h). In the Untreated group RPP was reduced from 152.4 +/- 7.3 to 113.6 +/- 5.8 and 83.0 +/- 4.4 mmHg during the first and second step respectively. RBF and GFR were only slightly reduced during the second step of reduced RPP. In control conditions V and UNa + V were greater in the denervated compared to the innervated kidney. The graded decrease in RPP reduced both V and UNa + V in the innervated as well as in the denervated kidney. In the Captopril group V and UNa + V were larger than in the Untreated group in both the innervated and the denervated kidney. A decrease of RPP similar to that observed in the Untreated group, produced similar haemodynamic changes. Also in the Captopril group the graded decrease in RPP reduced both V and UNa + V in the innervated as well as in the denervated kidney. Matching UNa + V against RPP values significant correlations were found in the innervated and denervated kidneys of both groups. Both renal denervation and ACE inhibition were accompanied by an increased gain of the pressure-natriuresis curve, but only renal denervation shifted the crossing of the pressure axis to the left. In the ACE inhibited animals renal denervation only shifted the curve to the left. In conclusion our data suggest that i) at each level of RPP renal nerves and angiotensin II decrease renal sodium excretion, ii) renal nerves and angiotensin II increase the slope of the renal function curve, iii) renal nerves shift to the right the renal function curve.

Electrophysiological evidence of ipsilateral reno-renal reflexes in the cat.

To verify the existence of ipsilateral reno-renal reflexes we studied the effect of surgical denervation of one kidney on the ipsilateral efferent renal nerve activity (ERNA), in the absence of contralateral afferent renal nerve activity. Thus the ipsilateral renal denervation was performed 1 h later than the contralateral renal denervation. The experiments were done on 9 anesthetized cats. Arterial pressure, urine flow rate (UFR) of both kidneys and ERNA to the ipsilateral kidney were measured. All variables were monitored during a 3 min control period and for 13 min after either contralateral and ipsilateral renal denervations. ERNA significantly increased (+20 +/- 9%) and UFR concomitantly decreased (-11 +/- 10%) after the surgical denervation of the contralateral kidney which showed an increase (+91 +/- 19%) in UFR. The subsequent ipsilateral denervation caused a significant increase in UFR (+117 +/- 25%) and ERNA (79 +/- 23%) of the same kidney, while on the opposite side UFR did not change. During the two procedures, arterial pressure did not change. Our data demonstrate the existence of ipsilateral reno-renal reflexes that exert a tonic inhibitory effect on ipsilateral ERNA.

Renal afferents responsive to chemical and mechanical pelvic stimuli in the rabbit.

1. Afferent nerve fibres sensitive to changes in the renal chemical environment have been found in the rat. To verify the existence of these fibres in the rabbit and their response pattern, afferent renal nerve activity was recorded during pelvic perfusions with NaCl solutions at different concentrations. 2. The experiments were carried out in 13 anaesthetized rabbits. Arterial pressure from a femoral catheter and afferent renal nerve activity from the distal stump of a cut renal nerve bundle were recorded. Three catheters were inserted into the renal pelvis to measure pelvic pressure, to allow pelvic perfusions at constant rates and to drain pelvic fluids. 3. After a control period, the pelvis was perfused with physiological saline (0.14 mol/l for 2 min), followed by one of a series of solutions containing increasing concentrations of NaCl (0.5, 0.75, 1.0 and 1.5 mol/l for 2 min). Pelvic perfusion was performed both at a low (0.2 ml/min) and a high (0.8 ml/min) flow rate for each solution tested. 4. In all animals arterial pressure was not modified during pelvic perfusions. Physiological saline did not change afferent renal nerve activity at the low perfusion rate, but it significantly increased afferent renal nerve activity and pelvic pressure at the high rate. Hypertonic NaCl solutions caused progressive increases in afferent renal nerve activity at both perfusion rates, and these effects were larger at the high perfusion rate. 5. These data demonstrate, in the rabbit, the existence of renal afferent nerves sensitive to discrete changes in pelvic ionic or osmotic concentration. The neural response is enhanced when renal mechano- and chemo-receptors are simultaneously activated.

Functional evidence of inhibitory reno-renal reflexes in spontaneously hypertensive rats.

The experiments were performed to study the role of the renal nerves and the reno-renal reflexes in the control of water and sodium excretion in spontaneously hypertensive rats (SHR) compared to their normotensive controls, Wistar Kyoto (WKY) rats. Unilateral renal denervation in anaesthetized animals produced a slight, progressive decrease in arterial pressure in both WKY and SHR rats. The glomerular filtration rate temporarily increased in the kidney that underwent the denervation in the SHR group only. After unilateral renal denervation a sharp increase in water and sodium excretion from the ipsilateral kidney was observed in both WKY and SHR. One hour after the denervation, the percent changes in water and sodium excretion were smaller in WKY (+32 +/- 19% and +24 +/- 17%) than in SHR rats (+84 +/- 15% and +93 +/- 20%). In the kidney contralateral to the denervation a reduction in water and sodium excretion was observed and this reduction was prompter in SHR than in WKY rats. One hour after the denervation, the percent changes in water and sodium excretion were similar in WKY (-21 +/- 8% and -18 +/- 7%) and SHR (-19 +/- 6% and -19 +/- 7%). In control groups, sham denervation did not cause significant changes in glomerular filtration rate, and urinary water and sodium excretion. Arterial pressure slightly and progressively decreased in both control groups. Electrical stimulation of the efferent renal nerves performed in WKY and SHR produced similar decreases in renal blood flow, glomerular filtration rate, and water and sodium excretion in the two groups for the same frequencies of stimulation. As this finding indicates that renal targets in hypertensive rats are normally responsive to the neural drive, our data demonstrate that renal responses to unilateral renal denervation in hypertensive rats are equal to the responses observed in normotensive rats. Our results indicate that tonically active inhibitory renorenal reflexes normally operate in spontaneously hypertensive rats.

Effects of adenosine-receptor agonists on renin release in anaesthetized rats.

OBJECTIVE: To investigate the effects of the interaction between adenosine receptors and renal nerves on renin release. MATERIALS AND METHODS: The effects on renin secretion of A1 (2-chloro-N6-cyclopentiladenosine) and A2 (2-hexynil-5'-N-ethyl-carboxamido-adenosine) adenosine-receptor agonists were studied in two groups of anaesthetized rats, each with one kidney surgically denervated. Arterial blood pressure and the renal blood flow of innervated and denervated kidneys were continuously recorded. Cannulae were inserted into both renal veins through femoral veins. After 1h of rest, A1 and A2 agonists were intravenously infused for 30 min in the two groups of rats. Plasma renin activity was measured by radioimmunoassay in blood samples drawn simultaneously from both renal veins and the femoral artery before and after the drug infusion. RESULTS: Infusions of A1 and A2 agonists produced comparable hypotensive effects. During A1 agonist administration, the heart rate decreased significantly, but it did not change after A2 agonist treatment. Renal blood flow was reduced by administration of the A1 agonist in both kidneys, while A2 agonist administration significantly reduced the renal blood flow of the innervated kidney only. The veno-arterial difference in plasma renin activity decreased after the A1 agonist infusion in both kidneys, but after the A2 agonist infusion it increased significantly in the innervated kidney only. CONCLUSIONS: Renal nerves do not influence the inhibition of renin release mediated by A1 adenosine receptors. In vivo, A2-receptor agonist administration can stimulate renin release only in the presence of intact renal nerves.

Renal afferents signaling diuretic activity in the cat.

Mechanoreceptors and chemoreceptors have been identified inside the kidney, but their functional role is still largely unclear. The aim of this study was to investigate whether changes in urine output could modify the discharge rate of renal afferent fibers. Experiments were performed in anesthetized cats in which afferent renal nerve activity (ARNA) was recorded by standard electrophysiological techniques from a centrally cut renal nerve. Arterial pressure, renal blood flow velocity, urine flow rate, and renal pelvic pressure were also measured. Three diuretic maneuvers were tested in the same cat: intravenous administration of physiological saline (8 to 13 mL/min for 2 minutes), furosemide (1 mg/kg), and atrial natriuretic peptide (ANP, 1 microgram/kg). The three maneuvers increased urine flow rate and pelvic pressure, respectively, 137.0 +/- 20.6% and 136.8 +/- 21.1% (saline), 148.6 +/- 31.7% and 139.6 +/- 43.5% (furosemide), and 75.9 +/- 7.9% and 62.1 +/- 21.2% (ANP) at the time of the maximum response. Arterial pressure slightly increased after saline, did not change after furosemide, and slightly decreased after ANP. Renal blood flow increased after saline and did not change after furosemide and ANP. The three maneuvers increased ARNA by 98.4 +/- 15.2% (saline), 270.7 +/- 100.8% (furosemide), and 59.6 +/- 23.4% (ANP). Changes in ARNA significantly correlate with changes in both pelvic pressure and urine flow rate. Our data demonstrate that increments in urine flow rate increase the firing rate of renal afferent fibers and suggest that (1) pelvic pressure is the major determinant of the neural response, and (2) this increased afferent discharge is due to activation of renal mechanoreceptors.

Interactions between the sympathetic nervous system and atrial natriuretic factor in the control of renal functions.

We studied neural influences on the renal actions of atrial peptides in anaesthetized cats by comparing the response to atrial natriuretic factor (ANF) infusion in the innervated kidney and in the contralateral surgically denervated kidney. During ANF infusion arterial pressure decreased, the heart rate did not change and blood flow to both kidneys increased slightly. Vascular conductances became slightly but significantly higher in the denervated kidneys than in the controls. In both kidneys, the glomerular filtration rate increased transiently and significantly. Inhibition of renin release was more prompt and larger in the innervated than in the denervated kidneys. ANF infusion caused a significant increase in sodium and water excretion from both the innervated and denervated kidneys. However, the diuretic and natriuretic effect in the innervated kidneys, although proportionally greater than that in the denervated kidneys, was of shorter duration and subsided after 20 min of ANF infusion. Efferent renal nerve activity did not change during the initial 10 min of ANF infusion but thereafter increased progressively and significantly. We conclude that the effects of atrial peptides on renin release and excretory functions are influenced by renal nerve activity.

Role of the renal nerves in the natriuretic response to vasopressin infusion.

The present study was designed to determine whether renal nerves influence the natriuretic response to an infusion of vasopressin. Experiments were performed on anaesthetized rats in which the response to vasopressin of the innervated kidney was compared with that of the contralateral surgically denervated kidney. During the vasopressin infusion the natriuretic effect was evident in both kidneys and was proportionally greater in the innervated kidney than in the denervated one. Efferent renal nerve activity, recorded in three additional animals, decreased during the vasopressin infusion. Our data demonstrate that the natriuretic response of the innervated kidney is larger than that of the denervated kidney, probably because of an associated decrease in efferent renal nerve activity.

Angiotensin converting enzyme inhibition and renin release from the kidney.

Experiments were performed in anaesthetized cats, to determine whether renal nerves interfere with the negative feedback action of angiotensin II (Ang II) on renin release. The increase in renin release from the innervated kidney in response to captopril-induced inhibition of Ang II generation was compared with the response of the contralateral denervated kidney. Renin release was measured before (control), and 5, 15 and 30 min after the beginning of captopril infusion (1 mg/kg priming dose followed by 1 mg/kg per h for 30 min intravenously), and 60 min after the end of the infusion. During the captopril treatment renin release from both kidneys increased, but after 15 and 30 min the increase in renin release from the innervated kidneys was significantly larger than that observed in the denervated kidneys. After the captopril infusion was stopped, renin release from both kidneys returned towards control values. These results could not be explained on the basis of the changes in renal haemodynamics, excretory functions and efferent renal nerve activity observed during the captopril infusion. The data suggest that the renal nerves influence the changes in renin release caused by captopril by increasing the sensitivity of juxtaglomerular cells to the negative feedback action of Ang II.

Neural, hemodynamic, and renal responses to stimulation of intestinal receptors.

Stimulation of visceral receptors with bradykinin has been shown to cause reflex increases in sympathetic nerve activity and systemic arterial pressure. In this investigation, serosal receptors of the intestine were stimulated by bradykinin in anesthetized cats to 1) compare mesenteric and renal sympathetic responses, 2) compare hemodynamic responses in mesenteric and renal beds, and 3) determine changes in renal function. This stimulation in intact animals caused pressor responses, significantly greater excitation of mesenteric than renal nerves, significantly greater mesenteric than renal vasoconstriction, diuresis, natriuresis, and, in denervated kidneys, increases in fractional sodium excretion. In vagotomized, sinoaortic-denervated cats, stimulation of intestinal receptors caused excitation of mesenteric nerve activity greater than renal for only 30 s. This sympathetic reflex response led to pressor responses, equal mesenteric and renal vasoconstriction, diuresis, natriuresis, and increased fractional excretion of sodium only in denervated kidneys. When abdominal perfusion pressure was held constant with an aortic snare in these same animals, the sympathetic reflexes initially caused greater mesenteric than renal vasoconstriction and antidiuresis and antinatriuresis only in innervated kidneys. These findings demonstrate that the intensity of hemodynamic and renal responses to stimulation of visceral receptors correlates well with the magnitude of sympathetic nerve responses.

Afferent pathways of neural reno-renal reflexes controlling sodium and water excretion in the cat.

We have studied the role of afferent renal nerve fibres in anaesthetized cats in mediating the decrease in sodium and water excretion from the contralateral kidney caused by unilateral renal denervation. Transient denervation of one kidney obtained by cooling of the left renal nerves increases contralateral efferent renal nerve activity and decreased sodium and water excretion from the opposite kidney. The results observed in animals with intact neural pathways were compared with those obtained after the left kidney had been selectively deafferentated by cutting the dorsal roots from T9 to L4. Bilateral section of dorsal roots did not affect the increase in sodium and water excretion from the transiently denervated left kidney, but entirely abolished the decrease in sodium and water excretion from the contralateral kidney. Neither the left nor the right dorsal root section alone, affected the response of the contralateral right kidney. Our data demonstrate that afferent renal nerve fibres project bilaterally to the spinal cord and form the afferent branch of the reno-renal reflex by which one kidney can control the function of the opposite one.

Renal reflexes in the regulation of blood pressure and sodium excretion.

The rich innervation of the kidney is distributed to all structures of renal parenchyma thus providing important anatomical support to the functional evidence that the renal nerves can control kidney functions and send signals on the kidney environment to the central nervous system. Efferent renal nerve fibres are known to influence renal haemodynamics by modifying arteriolar vascular tone, renin release by a direct action on juxtaglomerular cells, and the excretion of sodium and water by changing tubular reabsorption of sodium and water at the different tubular levels. Mechano- and chemo-receptors have been shown in the kidney. Afferent fibres connected with renal receptors convey signals to the central nervous system both at spinal and supraspinal levels. The central areas receiving inputs from the kidney are those involved in the control of cardiovascular homeostasis and fluid balance. Activation of renal receptors by the electrical stimulation of renal afferent fibres were found to elicit both excitatory and inhibitory sympathetic responses. Although the existence of excitatory renorenal reflexes has been suggested, electrophysiological and functional data demonstrate that neural renorenal reflexes exert a tonic inhibitory influence on the tubular sodium and water reabsorption and on the secretion of renin from the juxtaglomerular cells.

Cardiovascular effects of afferent renal nerve stimulation.

Electrical stimulation of afferent renal nerves elicits an increase in arterial pressure and heart rate. The hypertensive response is presumably due to the widespread activation of the sympathetic nervous system leading to peripheral vasoconstriction. Interestingly, the kidney does not appear involved in this reflex excitatory response to afferent renal nerve stimulation since changes in vascular conductances and excretory functions are equal in both the innervated and denervated kidney, and secondary to changes in renal perfusion pressure. In addition, no changes in renin release from either kidneys are observed during afferent renal nerve stimulation. It is likely that the electrical stimulation of afferent renal nerves activates other reflexes exerting an inhibitory influence on efferent renal nerve activity. Indeed, neural renorenal reflexes which tonically inhibit renal functions have clearly been demonstrated. Furthermore, preferential inhibition of efferent renal nerve activity by cardiopulmonary and sinoaortic receptors has recently been shown during activation of other visceral afferents.

Capsaicin treatment attenuates the reflex excitation of sympathetic activity caused by chemical stimulation of intestinal afferent nerves.

Sympathetic reflexes elicited by stimulation of visceral receptors have been well investigated, but the central neurotransmitters mediating these reflexes are largely unknown. Therefore, experiments were done to evaluate the role of substance P in the central transmission of a sympathoexcitatory reflex elicited by stimulation of intestinal receptors. Activity of mesenteric and renal nerves was recorded electrophysiologically in chloralose/urethane-anesthetized rats. Stimulation of intestinal receptors by serosal application of 0.5-1.0 microgram bradykinin increased mesenteric nerve activity by 100 +/- 21%, renal nerve discharge by 33 +/- 9%, and systemic arterial pressure by 10 mm Hg. Chronic capsaicin treatment (cumulative dose 950 mg/kg) caused a 52% depletion of substance P-like immunoreactivity from dorsal root ganglia and a significant attenuation of these reflexes. Mesenteric nerve activity increased by 48 +/- 6% in the capsaicin-treated rats. Bradykinin did not cause significant changes in renal nerve activity or systemic arterial pressure in these rats. The excitation of mesenteric nerve activity was significantly greater than the increase in renal nerve activity int he untreated and capsaicin-treated rats; capsaicin treatment affected responses of both nerves similarly. Capsaicin treatment did not have generalized effects on sympathetic reflexes, as mesenteric and renal nerve activities were decreased by baroreceptor activation similarly in the untreated and capsaicin-treated rats. These results suggest that the central transmission of the reflex response to intestinal receptor stimulation is mediated in part by substance P or other capsaicin-sensitive peptides.