Kidney transplantation improves baroreceptor sensitivity

Kidney transplant recipients as well as patients on hemodialysis frequently share an increased risk of cardiovascular diseases. Besides other factors, modulations in central neural blood pressure regulation have to be considered as a pathogenetic factor. In this study, baroreceptor function as a possible modulator of blood pressure and the activity of the generating components of the sympathetic nervous system were estimated in 20 kidney transplant recipients, 20 normotensive patients on hemodialysis and 20 age-matched volunteers using the sequence analysis technique and Fast Fourier Transformation (FFT). No blood pressure differences could be measured (83.7 ± 2.5 vs. 82.5 ± 3.8 vs. 79.2 ± 2.4 mm Hg). Pulse interval-blood pressure sequences and the slope of Δ pulse interval/Δ mean arterial blood pressure of these sequences, representing baroreceptor sensitivity, did not differ between kidney transplant recipients and controls (11.2 ± 1.4 vs. 13.4 ± 1.3 ms/mmHg), whereas in hemodialysis patients a reduced baroreceptor sensitivity (5.2 ± 1.2 ms/mmHg) was detected. The 66–129 mHz component (Mayer waves) of heart rate and blood pressure spectrum in normals (650 ± 57 and 630 ± 70 modulus) significantly (p < 0.05) exceeded its equivalent in kidney transplant recipients (430 ± 32 and 452 ± 27 modulus) and patients on hemodialysis (375 + 38 and 394 ± 40 modulus). In conclusion, our study provided evidence that both in kidney transplant and dialysis patients a decreased activity of the generating compounds of the sympathetic nervous system can be detected as compared to healthy volunteers. In contrast to hemodialysis patients, the baroreceptor sensitivity is unaffected in kidney transplant recipients and may, therefore, not contribute to the development of cardiovascular diseases.     

Digitalis and baroreceptor reflexes in man

Data in animals indicate that large amounts of digitalis potentiate arterial baroreflexes and that this factor may be important for the cardiovascular effects of the drug. To determine if arterial baroreflex potentiation also exists after administration of therapeutic doses of digitalis in man, we studied how stimulation and deactivation of arterial baroreceptors by phenylephrine and nitroglycerin injection affect heart rate and how stimulation and deactivation of carotid baroreceptors by neck suction and pressure affects blood pressure and heart rate. The study was performed in 29 normotensive or hypertensive subjects before and after injection of Lanatoside C (0.8 mg i.v.). Baroreceptor stimulation reduced heart rate and blood pressure, while baroreceptor deactivation increased both of these variables. The bradycardic and hypotensive effect of baroreceptor stimulation increased significantly after digitalis both in normotensive and hypertensive subjects. However, the tachycardic and hypertensive responses to baroreceptor deactivation were not affected by digitalis. Thus, therapeutic doses of digitalis in man enhance baroreceptor reflexes, and both the heart rate and the blood pressure reflex effects are involved. However, the enhancement occurs to a marked degree only with baroreceptor stimulation and is not evident with baroreceptor deactivation.     

Rapid baroreceptor resetting in Dahl salt-sensitive rats

Dahl salt-sensitive rats rapidly become hypertensive when exposed to a high salt diet, but Dahl salt-resistant rats maintain normal blood pressure on a high salt diet. A defect in baroreceptor afferents is thought to play a key role in the low sensitivity of baroreceptor reflexes in Dahl salt-sensitive rats even in the prehypertensive stage during low salt treatment. In the present study, we tested whether differences in rapid resetting ability might contribute to differences in baroreceptor function in Dahl rats. Four groups of rats were tested: salt-sensitive and salt-resistant rats on low salt and high salt diets (0.15% and 8.0% NaCl). We compared the rapidly resetting responses of baroreceptors from each group using an in vitro preparation. Rapid resetting was assessed for each aortic baroreceptor (n = 46) by linear fit of the relation of pressure threshold and conditioning mean arterial pressure. Each group had a wide range of resetting ratios (the slope of the resetting relation). Despite higher initial pressure thresholds in salt-sensitive rats on a high salt diet, resetting ratios among the four groups were similar. Thus, the ability of Dahl salt-sensitive baroreceptors to rapidly reset is preserved, despite high dietary salt and a genetic predisposition to dysfunction. The present findings in Dahl rats reinforce the results of recent studies of rapid resetting during spontaneous and renal hypertension, which suggests that the rapid resetting process is remarkably resistant to factors that compromise baroreceptor function.     

Carotid sinus baroreceptor sensitivity in experimental heart failure

Single-unit carotid sinus baroreceptor activity was recorded in normal and heart-failure (pacing-induced) dogs. The sensitivity of these units was compared between the two groups of dogs. After development of clinical heart failure, the animals were anesthetized, and the left carotid sinus was vascularly isolated and perfused with oxygenated Krebs-Henseleit solution. Single-unit baroreceptor discharge was recorded from the carotid sinus nerve in response to stepwise increases in carotid sinus pressure (CSP). In addition, the carotid sinus diameter was measured with sonomicrometer crystals. In this way, both CSP-discharge and CSP-diameter curves were constructed for both normal and heart-failure dogs. Analysis of these curves demonstrated that the heart-failure group exhibited a significant decrease in peak discharge (48.1 +/- 3.0 vs. 22.2 +/- 2.2 spikes/sec; p less than 0.001) and a significant elevation in threshold pressure compared with the normal animals (91.0 +/- 5.0 vs. 119.1 +/- 4.4 mm Hg; p less than 0.001). The peak slope of the CSP-discharge curve was also significantly lower in the heart-failure group (0.63 +/- 0.06 vs. 0.40 +/- 0.09 spikes/sec/mm Hg; p less than 0.05). In the heart-failure group, perfusion of the carotid sinus with ouabain (0.01 micrograms/ml) caused a significant decrease in threshold pressure and a significant increase in peak discharge frequency, as well as an increase in slope of the CSP-discharge curve. There were no changes in CSP-diameter relations in response to ouabain. This dose of ouabain had no effect on pressure-discharge relations or carotid sinus diameters in normal dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aldosterone reduces baroreceptor discharge in the dog.

We have previously demonstrated that baroreceptor discharge sensitivity is depressed in dogs with experimental heart failure and that this depressed sensitivity can be reversed by the Na+,K(+)-ATPase inhibitor ouabain. This suggests that enhanced Na+,K(+)-ATPase activity in baroreceptors is responsible for the blunted baroreceptor discharge sensitivity seen in heart failure state. Because aldosterone, a known stimulator of Na+,K(+)-ATPase, is elevated in heart failure the present study was undertaken to determine the effects on baroreceptor discharge of perfusion of the carotid sinus with aldosterone in normotensive dogs. Single unit baroreceptor activity was recorded as well as carotid sinus pressure and the diameter of the carotid sinus. Perfusion of the carotid sinus with aldosterone (in Krebs-Henseleit solution) significantly elevated threshold pressure (108.5 +/- 3.1 mm Hg versus 92.7 +/- 4.6 mm Hg, p less than 0.05) and reduced peak discharge rate (40.3 +/- 3.9 spikes/sec, p less than 0.05). These effects appeared 15 minutes after aldosterone perfusion and remained constant for the next 60 minutes. There was no change in the carotid sinus pressure-diameter curve during perfusion with aldosterone. Perfusion of the carotid sinus with ouabain (0.1 microgram/ml) during aldosterone perfusion did not reverse the blunted baroreceptor discharge. The blunted baroreceptor activity induced by perfusion of the carotid sinus with aldosterone was prevented by removal of the endothelial cells in the carotid sinus area with a balloon-tipped catheter or by perfusion with saponin. Finally, perfusion of the carotid sinus with spironolactone (10 ng/ml), a mineralocorticoid receptor antagonist, prevented the inhibitory effect of aldosterone. These data suggest that aldosterone reduces maximum baroreceptor discharge.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired arterial baroreceptor sensitivity before tilt-induced syncope.

Autonomic dysfunction seems to play a central role in the pathophysiology of neurocardiogenic syncope (NCS) but conflicting data have recently become available. We evaluated autonomic nervous system (ANS) function (heart rate variability (HRV), systolic blood pressure variability (SBPV) and baroreceptor gain (BRG)) and non-invasive haemodynamics (cardiac output and total peripheral resistance) in patients with neurocardiogenic syncope. Retrospectively, we evaluated 12 NCS patients (positive head-up tilt without pharmacological provocation) in the basal state and at initial tilt, 12 non-NCS patients with tilt-negative syncope and 12 aged-matched normal controls. Prospectively, we evaluated 16 NCS patients to analyse the haemodynamics and ANS activity throughout the tilt test (beginning of tilt and before syncope occurs). HRV and SBPV were accessed by fast Fourier transforms (FFT) and spontaneous BRG by temporal sequences, slope and a index. Modelflow was used to quantify the non-invasive haemodynamics. None of the autonomic and haemodynamic parameters at baseline or in the first 10 min of tilt was different among the respective NCS, non-NCS syncope and normal control groups, except for SBP, which was higher at baseline in controls. Throughout the tilt test in the prospective NCS group, the heart rate increased (88-95 beats x min(-1), P<0.05), systolic blood pressure decreased (123-109 mmHg, P<0.01), and arterial baroreceptor gain was reduced (7.6 to 5.5 ms mmHg(-1), P<0.01) and the absolute high frequency component of HRV (HF HRV) decreased (150-80 ms(-2), P<0.05), before syncope occurred. There was no change in the low frequency component of HRV (LF HRV), SBPV, cardiac output (CO) or total peripheral resistance (TPR). Tilt-induced syncope could not be predicted by non-invasive haemodynamic or autonomic parameters at rest or in the initial minutes of tilt. The decrease in arterial baroreceptor gain could be a precocious expression of the transient autonomic dysfunction that characterizes the occurrence of neurocardiogenic syncope.     

Roles of arterial baroreceptor reflex during bezold-jarisch reflex

Among the many cardiopulmonary reflexes, this review specifically examines the roles of the arterial baroreflex during the Bezold-Jarisch reflex (BJR). Activation of cardiopulmonary vagal afferent C-fibers induces hypotension, bradycardia, and apnea, which are known collectively as the BJR; myocardial ischemia and infarction might induce the BJR. Arterial baroreflex has been established as an important negative feedback system that stabilizes arterial blood pressure against exogenous pressure perturbations. Therefore, understanding the functions of the arterial baroreflex during the BJR is crucial for elucidating its pathophysiological implications. The main central pathways of the BJR and the baroreflex are outlined herein, particularly addressing the common pathway between the reflexes. Furthermore, the pathophysiological roles of the arterial baroreflex during the BJR are described along with a brief discussion of pathophysiological merits and shortcomings of the reflexes.     

Acute hypoxemia increases cardiovascular baroreceptor sensitivity in humans

BACKGROUND: We postulated that acute hypoxemia increases susceptibility to orthostatic hypotension by increasing the sensitivity of cardiovascular baroreceptors. METHODS: Hemodynamics were measured noninvasively in 17 healthy, normotensive subjects while being subjected to decreasing venous return by exposure to lower body negative pressure (LBNP) and breathing either a normobaric normoxic (21% O2) or normobaric hypoxic (12% O2) gas mixture. RESULTS: Hypoxia variably decreased hemoglobin saturation (in percent+/-SEM, from 99%+/-1% to 87%+/-2%, P<.01). Incremental increases in LBNP to -50 mm Hg significantly lowered systolic blood pressure (BP), pulse pressure (PP), forearm blood flow (FBF), and increased heart rate (HR). Hypoxia significantly increased baseline systolic BP, PP, and HR. The maximum change in HR in response to LBNP-induced reductions in PP increased during acute hypoxemia (maximum DeltaHR/DeltaPP, in +/-SEM) from 1.32+/-0.18 beats/min/mm Hg v 1.91+/-0.25 beats/min/mm Hg, P<.05. Those subjects who had the most hemoglobin desaturation during hypoxia, when compared to those subjects who desaturated minimally, had greater systolic BP at rest (128+/-3 mm Hg v 114+/-3 mm Hg, P=.05) and during LBNP (115+/-4 mm Hg v 100+/-1 mm Hg, P=.01). CONCLUSIONS: Acute hypoxia increased compensatory HR responses to LBNP-dependent reductions in BP. Those normotensive individuals with higher BP at rest and during LBNP developed greater degrees of hypoxia-induced hemoglobin desaturation. Patients with sleep apnea with periods of hypoxemia are prone to hypertension; more important, patients with higher BPs also demonstrate greater degrees of hypoxia-induced desaturation of oxyhemoglobin.     

Effect of arterial baroreceptor denervation on sodium balance

During chronic increased dietary sodium intake, arterial baroreceptors buffer against sustained increases in arterial pressure, and renal sympathoinhibition contributes importantly to the maintenance of sodium balance by decreasing renal tubular sodium reabsorption and increasing urinary sodium excretion. The present study examined the effect of arterial baroreceptor denervation on sodium balance in conscious rats during low, normal, and high dietary sodium intake. Compared with measurements made before arterial baroreceptor denervation, arterial baroreceptor-denervated rats had similar sodium balance during normal dietary sodium intake but significantly more negative sodium balance during low dietary sodium intake and significantly more positive sodium balance during high dietary sodium intake. At the end of the high dietary sodium intake period, arterial pressure (under anesthesia) was 159+/-5 mm Hg after arterial baroreceptor denervation and 115+/-1 mm Hg before arterial baroreceptor denervation. Sham arterial baroreceptor denervation in time control rats had no effect on sodium balance or arterial pressure during the different dietary sodium intakes. These studies indicate that (1) arterial baroreceptor denervation impairs the ability to establish sodium balance during both low and high dietary sodium intake, and (2) arterial baroreceptor denervation leads to the development of increased arterial pressure during high dietary sodium intake in association with increased renal sodium retention.     

Carotid baroreceptor reflex coronary vasodilation in the dog

The hypothesis that neurally mediated coronary vasodilation occurs as part of the carotid baroreceptor reflex was investigated. The left main coronary artery was cannulated and perfused at constant pressure (100 mm Hg) in closed-chest, chloralose-anesthetized dogs. The heart was paced at a constant rate between 60 and 70 beats/min after atrioventricular heart block. Propranolol (1 mg/kg) was given to prevent beta-receptor-mediated alterations in contractility. Aortic blood pressure was stabilized with a blood reservoir. The aortic depressor nerves were cut bilaterally to prevent the buffering influence of aortic arch baroreceptors on the carotid baroreceptor reflex. The carotid sinuses were vascularly isolated and perfused with arterial blood at controlled pressures. Under these conditions, a step change in carotid sinus pressure from 70 to 210 mm Hg produced a 0.29 ml/min per g increase in coronary flow above control and a 10 mm Hg increase in coronary sinus blood oxygen tension. A step in carotid sinus pressure from 70 to 150 mm Hg resulted in a flow increase of 0.13 ml/min per g and a coronary sinus oxygen tension increase of 5.3 mm Hg relative to prestimulation values. Atropine (0.5 mg/kg, iv) blocked most of the reflex coronary vasodilation, indicating a parasympathetic component, and the addition of adrenergic alpha-receptor blockade with phenoxybenzamine (0.25 mg/kg, ic) abolished the remaining response, demonstrating sympathetic participation. The reflex nature of the coronary response was confirmed with carotid sinus denervation and vagotomy. It is concluded that carotid sinus hypertension results in a graded reflex neural coronary vasodilation independent of myocardial metabolic factors. The major component is due to activation of parasympathetic coronary vasodilator fibers, but there is also inhibition of sympathetic vasoconstrictor fibers.