Control Of Renal Sympathetic Nerve Activity Research Articles

Reflex control of renal sympathetic nerve activity in heart failure is preserved in ovary intact female rats (1171.3)

Following myocardial infarction (MI), pathological increases in sympathetic nerve activity (SNA) drive the development and progression of heart failure. The current study investigated the effects of female sex and ovarian hormones on arterial baroreflex and cardiac sympathetic afferent reflex (CSAR) control over renal SNA in MI‐induced heart failure. 6 weeks post MI or sham surgery , arterial pressure and renal SNA responses were recorded in chloralose‐urethane anesthetized male, female and ovariectomized female (OVX) rats. In male and OVX MI groups, arterial baroreflex control of renal SNA was significantly impaired compared to shams, due mostly to an impaired ability to inhibit SNA. In ovary‐intact females, arterial baroreflex control of renal SNA was unaltered in MI animals compared to sham. CSAR mediated increases in renal SNA were significantly augmented in male and OVX MI groups when compared to ovary‐intact female MI group. The current study is the first to describe a protective effect of ovarian hormones on reflex control of SNA in MI‐induced heart failure.Grant Funding Source: Lottery Health New Zealand and University of Auckland Faculty Research Development Fund

Hypothalamic mTORC1 Signaling Controls Sympathetic Nerve Activity and Arterial Pressure and Mediates Leptin Effects

The fundamental importance of the hypothalamus in the regulation of autonomic and cardiovascular functions is well established. However, the molecular processes involved are not well understood. Here, we show that the mammalian (or mechanistic) target of rapamycin (mTOR) signaling in the hypothalamus is tied to the activity of the sympathetic nervous system and to cardiovascular function. Modulation of mTOR complex 1 (mTORC1) signaling caused dramatic changes in sympathetic traffic, blood flow, and arterial pressure. Our data also demonstrate the importance of hypothalamic mTORC1 signaling in transducing the sympathetic and cardiovascular actions of leptin. Moreover, we show that the PI3K pathway links the leptin receptor to mTORC1 signaling and that changes in its activity impact sympathetic traffic and arterial pressure. These findings establish mTORC1 activity in the hypothalamus as a key determinant of sympathetic and cardiovascular regulation and suggest that dysregulated hypothalamic mTORC1 activity may influence the development of cardiovascular diseases.

Baroreflex control of renal sympathetic nerve activity in mice with cardiac hypertrophy

Altered renal sympathetic nerve activity (RSNA) plays a major role in the progression of cardiac hypertrophy. We aimed to evaluate the baroreflex control of RSNA in mice with cardiac hypertrophy. Swiss Webster mice were treated with isoproterenol (15 μg/g/day, s.c.) or vehicle and the baroreflex evaluation was performed by measuring changes in RSNA in response to changes in arterial pressure. The maximal gain of the reflex changes in RSNA was reduced in isoproterenol-treated animals (1.39 ± 0.08%/mm Hg) in comparison with vehicle-treated animals (1.77 ± 0.10%/mm Hg). Therefore, we can conclude that cardiac hypertrophy led to a reduced sensitivity of baroreflex control of RSNA.

Effects of sex and ovarian hormones on the initial renal sympathetic nerve activity response to myocardial infarction

The physiological mechanisms contributing to sex differences following myocardial infarction (MI) are poorly understood. Given the strong relationship between sympathetic nerve activity (SNA) and outcome, we hypothesized there may be a sex difference in SNA responses to MI. In anaesthetized, open-chest male, female and ovariectomized (OVX) female Wistar rats, mean arterial pressure, heart rate and renal SNA were recorded in response to ligation of the left coronary artery. In males, renal SNA increased by 30 ± 6% in the first minute of coronary occlusion (P < 0.05) and remained elevated at 18 ± 7% above baseline (P < 0.05) at 2 h following MI. In response to MI, ovary-intact females displayed no change in renal SNA, whereas OVX females displayed a significant increase, similar to that seen in the males (increases of 43 ± 11% at 1 min and 21 ± 7% at 2 h post-MI, P < 0.05 versus intact females). Arterial baroreflex control of renal SNA had a smaller range in females (ovary intact and OVX) than males; no changes in arterial baroreflex responses were observed 1 h post-MI in males or females. Denervating the arterial baroreceptors abolished the renal SNA response to MI in the males, whereas in ovary-intact females and OVX females the response was unaltered. These findings suggest that ovarian hormones are able to blunt the initial sympathetic activation post-MI in females and that the importance of the arterial baroreflex in mediating initial sympathetic activation post-MI is different between the sexes.

Baroreflex and somato-reflex control of blood pressure, heart rate and renal sympathetic nerve activity in the obese Zucker rat

It has been reported that the baroreflex control of heart rate (HR) and sympathetic nerve activity (SNA) is attenuated in obese Zucker rats (OZRs) compared with age-matched lean animals (LZRs). What is not known, however, is the extent to which the baroreflex control of mean arterial blood pressure (MAP) is altered in the OZR. In addition, it is not known whether the interactions of other sensory nerve inputs on autonomic control are altered in the OZR compared with the LZR. The aim of this study was to determine the baroreflex control of MAP, HR and renal SNA (RSNA) in the OZR and LZR using an open-loop baroreflex approach. In addition, the effect of brachial nerve stimulation (BNS) on the baroreflex control was determined in these animals. Age-matched, male LZRs and OZRs were anaesthetized, and the carotid baroreceptors were vascularly isolated, bilaterally. The carotid sinus pressure was increased in 20 mmHg increments from 60 to 180 mmHg using an oscillating pressure stimulus. Baroreflex function curves were constructed using a four-parameter logistic equation, and gain was calculated from the first derivative, which gave a measure of baroreceptor sensitivity, before and during BNS. The range over which the baroreflex could change MAP (28 ± 6 versus 87 ± 5 mmHg; mean ± SEM), HR (17 ± 4 versus 62 ± 11 beats min(-1)) and normalized RSNA (NormNA; 22 ± 4 versus 76 ± 11%) was significantly decreased in the OZR compared with the LZR. Likewise, the maximal gain was lower in the OZR, as follows: MAP -0.88 ± 0.22 versus -2.26 ± 0.17; HR -0.42 ± 0.18 versus -1.44 ± 0.22 beats min(-1); and NormNA -0.54 ± 0.14 versus -1.65 ± 0.30% mmHg(-1). There was no difference in the mid-point of the baroreflex curve for each variable between the OZR and LZR. However, the minimal values obtained when the baroreceptors were maximally loaded were higher in the OZR (MAP 68 ± 5 versus 53 ± 4 mmHg; HR 455 ± 7 versus 390 ± 13 beats min(-1); and NormNA -19 ± 4 versus -48 ± 8%). Brachial nerve stimulation in the LZR resulted in an upward and rightward resetting of the baroreflex control of MAP and RSNA, and abolished baroreflex control of HR. The baroreflex control of RSNA in the OZR during BNS was further attenuated and reset upwards and to the right, while the HR response was abolished. With respect to MAP, the baroreflex curve reset upwards and to the right to a point comparable with the LZR during BNS. These data show that there is an attenuated baroreflex control in the OZR and that the ability to reset to higher arterial pressure during somatic afferent nerve stimulation is similar to that in the LZR.

Dynamic arterial baroreflex function during high intensity exercise in humans: insights into sympathetic control

Dynamic arterial baroreflex function during high intensity exercise in humans: insights into sympathetic control

Blockade of brain 'ouabain' prevents the impairment of baroreflexes in rats after myocardial infarction.

The purpose of this study was to test whether increased brain "ouabain" contributes to impairment of both arterial and cardiopulmonary baroreceptor reflexes in congestive heart failure (CHF). Two to 5 days after coronary artery ligation (MI) or sham surgery in male Wistar rats, chronic intracerebroventricular (ICV) infusion was started with either antibody Fab fragments, which bind ouabain and related steroids with high affinity, or gamma-globulins as control (200 microg x 12 microL[-1] x d[-1] for both) with osmotic minipumps implanted subcutaneously. After 8 weeks of infusion, in conscious rats, mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), and renal sympathetic nerve activity (RSNA) were recorded at rest and in response to ramp changes in blood pressure (BP) induced by intravenous phenylephrine and nitroprusside and to changes in CVP elicited by acute volume expansion with 5% dextrose. Compared with sham rats, in MI rats with ICV gamma-globulins, resting MAP was significantly lower and CVP increased, and both arterial and cardiopulmonary baroreflex control of RSNA and HR were attenuated. ICV Fab fragments prevented the decrease in resting BP and largely prevented impairment of arterial and cardiopulmonary baroreflex control of both RSNA and HR. These data indicate that increased brain ouabain plays a major role in the impairment of baroreflexes in rats with CHF after myocardial infarction.

Multifiber renal SNA recordings predict mean arterial blood pressure in unanesthetized rat

The goal of this analysis was to quantify the relationship between renal sympathetic nerve activity (SNA) and mean arterial blood pressure (MAP). We previously recorded renal SNA and MAP in conscious rats during a stressful behavioral stimulus and during a nonstressful stimulus. We then formulated a set of two linear, first-order differential equations that uses our SNA recordings after a time delay (the input) to predict fluctuations in MAP (the output). Our model has four parameters: 1) the cardiovascular time constant T that characterizes the frequency response function between the effector elements controlled by the sympathetic nerves and the cardiovascular system (1-5 s); 2) the effector time constant Te determined by the coupling between the sympathetic nervous system and the effectors (0.0-0.6 s); 3) the efferent time delay tau e between a change in SNA and a change in MAP (0.4-0.6 s); and 4) a proportionality constant C between fluctuations in SNA and fluctuations in MAP (0.3-3.4 mmHg/nV). The parameters of the model were determined that minimize the residual error between the simulated time series and the actual data time series for a stressful stimulus. Then we tested the ability of the transfer function to predict the MAP response to a nonstressful stimulus. In five of seven rats tested, the model's predictions were good, with mean cross-correlation coefficients for the predicted trials between 0.62 and 0.83. We show that multifiber renal SNA recordings can reliably predict changes in MAP in the unanesthetized rat. Thus the overall sympathetic drive to the cardiovascular system is indexed by renal SNA, although the vasomotor effectors driven by renal SNA control only approximately 20% of the blood cow.

Antagonism of vasopressin V1 receptors in NTS attenuates baroreflex control of renal nerve activity.

Previous work has shown that arginine vasopressin (AVP) present in the nucleus tractus solitarius (NTS) contributes to the control of peripheral cardiovascular parameters such as arterial pressure, heart rate, and sympathetic activity. In this study, we attempted to elucidate the influence of AVP in the NTS on baroreflex control of mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in urethan-anesthetized rats. To test the baroreflex, the aortic depressor nerve (ADN) was stimulated over a range of frequencies (1-15 Hz) to produce frequency-response curves for MAP and RSNA. The vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)]AVP (aAVP) was microinjected bilaterally or unilaterally into the caudal NTS to eliminate the influence of endogenous AVP on decreases in MAP and RSNA elicited by ADN stimulation. Bilateral microinjection of 10 or 100 ng aAVP significantly attenuated the decreases in RSNA elicited by ADN stimulation. Decreases in MAP were only attenuated following bilateral microinjection of 100 ng aAVP. Unilateral microinjection of the same doses of aAVP did not influence baroreflex control of MAP or RSNA. These results indicate that endogenous AVP within the NTS contributes to cardiovascular regulation. They also suggest that AVP within the NTS may specifically influence baroreflex control of RSNA.

Impairment of cardiopulmonary baroreflexes during the newborn period

The present study was designed to characterize the maturation of cardiopulmonary reflex control of renal sympathetic nerve activity (RSNA) independent of influences from the arterial baroreflex. Studies were conducted in conscious newborn lambs (3- to 7-days-old) (n = 16) and older lambs (6- to 8-wk-old) (n = 18). All animals underwent either sinoaortic denervation (SAD) or a sham procedure. Hemodynamic, humoral, neural, and renal responses to volume expansion (6% Dextran 70, 0.7 ml.kg-1.min-1 x 60 min) were recorded. Volume expansion resulted in a significant decrease (P < 0.05) in RSNA in intact newborn (-28.1 +/- 5.3% change from control) and older lambs (-19.4 +/- 10.1%). SAD totally abolished the sympathetic inhibition seen with volume expansion in newborn lambs (-3.6 +/- 5.7%) but not in older lambs (-25.6 +/- 8.4%). Right atrial pressure increased in a similar fashion in both newborn (intact: 5.6 +/- 0.5 mmHg; SAD: 6.1 +/- 0.8 mmHg) and older lambs (intact: 5.2 +/- 0.9 mmHg; SAD: 5.3 +/- 0.9 mmHg) and was not altered by SAD. The reflex bradycardia seen with volume expansion in newborn lambs was blocked by SAD. The present study demonstrates that, during the newborn period, the RSNA and heart rate responses to volume expansion are dependent mainly on the integrity of the arterial baroreflex. Furthermore, these studies suggest that cardiopulmonary reflex control of RSNA in response to volume expansion is impaired early in life and increases with maturation.

Dietary Na+ and cardiopulmonary baroreflex control of renal sympathetic nerve activity in SHR

In young Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with or without chronic sinoaortic denervation (SAD), we evaluated the effects of low, regular, and high dietary sodium intake (L-Na, R-Na, and H-Na, respectively) from 4 to 8 wk of age on cardiopulmonary baroreflex function, which was assessed by changes in renal sympathetic nerve activity (RSNA) and heart rate (HR) in response to acute volume expansion. In intact SHR H-Na increased blood pressure (BP), whereas L-Na decreased BP. No changes were observed in intact WKY. The gain of the cardiopulmonary baroreflex control of both HR and RSNA was significantly attenuated in SHR vs. WKY on R-Na. In both SHR and WKY, L-Na had no effects on the gain of RSNA and HR responses. In both strains, H-Na did not affect the gain of HR but attenuated the gain of the RSNA response. H-Na attenuated the gain of RSNA response more in SHR with SAD vs. intact SHR (52 vs. 69% of corresponding R-Na control) but less in WKY with SAD vs. intact WKY (80 vs. 71% of corresponding R-Na control). These data indicate that in SHR, H-Na further desensitizes the already impaired cardiopulmonary baroreflex control of RSNA. After SAD, this attenuation is more prominent in SHR but becomes less prominent in WKY. High sodium intake, therefore, modulates the interaction between the arterial and cardiopulmonary baroreflexes in the control of RSNA oppositely in WKY vs. SHR.

Vagal cardiopulmonary reflexes after left ventricular deafferentation.

Cardiac transplantation and chronic myocardial infarction interrupt vagal afferent nerve fibers, which originate mainly from the ventricles. Marked abnormalities of reflexes mediated by cardiopulmonary receptors with vagal afferent fibers have been demonstrated after both cardiac transplantation and chronic myocardial infarction. The relation between these reflex abnormalities and ventricular deafferentation is not known. To further assess this relation, we investigated the effects of left ventricular (LV) deafferentation on the control of renal sympathetic nerve activity (RSNA) by the vagal cardiopulmonary reflex in chloralose-anesthetized, mechanically ventilated dogs with sinoaortic denervation. Responses of left atrial pressure (LAP) and RSNA to hemorrhage and volume expansion were measured before and after application of 88% phenol to either the inferoposterior LV (n = 12) or the entire LV (n = 14). In control experiments, measurements were made before and after application of saline to the LV (n = 12). Reflex sensitivity (percent change in RSNA per mm Hg change in LAP) measured during volume expansion was mildly attenuated after both total (prephenol, -9.1 +/- 0.7; postphenol, -6.6 +/- 0.7; P < .05) and inferoposterior (pre, -12.5 +/- 1.8; post, -8.1 +/- 0.6; P = .055) LV deafferentation. Reflex sensitivity measured during hemorrhage was not significantly altered by inferoposterior or total LV deafferentation. Epicardial saline had no significant effect on reflex sensitivity values measured during either volume expansion or hemorrhage. Reflex inhibition of RSNA in response to intracoronary nicotine was abolished after phenol application, indicating adequate ventricular deafferentation. Phenol application had no significant effect on LAP-myocardial segment length relations measured by sonomicrometry (n = 6). Interruption of vagal afferent input from the LV has only modest effects on the control of RSNA by the vagal cardiopulmonary reflex. These data indicate that there is considerable redundancy in the vagal cardiopulmonary reflex such that receptors from the lungs and other cardiac chambers can largely compensate for the loss of afferent input from the LV.

Effect of exercise training on RSNA, baroreflex control, and blood pressure responsiveness

The effect of exercise training (ET) on renal sympathetic nerve activity (RSNA), baroreflex control of RSNA and heart rate (HR), and arterial pressure (AP) responsiveness to phenylephrine and angiotensin II (ANG II) was studied in six trained (T) and six sedentary (S) male Wistar rats. ET was performed on a motor treadmill for 13 wk. The RSNA signals of unanesthetized rats were processed by an analog-to-digital converter to quantify the nerve discharges associated with changes in AP and HR. The reflex control of RSNA and HR were evaluated during progressive injections of phenylephrine and sodium nitroprusside. Mean arterial pressure (MAP) was similar in both groups. RSNA was significantly lower in T rats (28 +/- 2 vs. 36 +/- 3%). T rats had an impairment of baroreflex control of RSNA in response to nitroprusside (4.9 +/- 0.89 vs. 12.3 +/- 1.2 bars.cycle-1.mmHg-1). ET decreased AP responsiveness for phenylephrine and ANG II. Therefore ET produces 1) no change in resting MAP but a significant decrease in RSNA and AP responsiveness and 2) partial impairment of baroreflexes, i.e., bradycardic responses and RSNA during MAP decrease.

Dietary Na, age, and baroreflex control of heart rate and renal sympathetic nerve activity in rats.

Heart rate (HR) and renal sympathetic nerve activity (RSNA) responses to ramp changes in blood pressure (BP) by (de)pressor agents and to acute volume expansion were recorded in conscious young, mature, and old Wistar rats maintained for 4 wk on diets containing low, control, or high dietary Na. Both HR and RSNA responses to BP increases or decreases were attenuated on low-Na diet compared with control Na diet. On high-Na diet, HR responses to BP changes and RSNA responses to BP increases were also attenuated, but in contrast the excitatory response of RSNA to BP decreases was augmented. The inhibitory RSNA response, but not the HR response, to volume expansion was significantly attenuated in young rats on high-Na diet but not on low-Na diet. The effects of both low and high dietary Na on HR and RSNA responses were most marked in young rats, less in mature rats, and even less in old rats. These results indicate a discordance of high dietary Na-induced changes in HR vs. RSNA control by the arterial and cardiopulmonary baroreflex, which is suggestive of central mechanisms affected by dietary Na. The developing nervous system appears to be the most responsive to dietary Na.

Increase in sympathetic activity with age. II. Role of impairment of cardiopulmonary baroreflexes

We have previously shown that arterial baroreflex function is significantly impaired in a group of old beagles [G. Hajduczok, M. W. Chapleau, S. L. Johnson, and F. M. Abboud. Am. J. Physiol. 260 (Heart Circ. Physiol. 29): H1113-H1120, 1991]. In the present study, we determined whether the neural limb of the cardiopulmonary baroreflex control of renal sympathetic nerve activity (RSNA) and the interaction between the arterial and cardiopulmonary reflexes is also impaired with senescence. In the anesthetized state, the aortic nerves were sectioned and carotid sinuses were isolated bilaterally with carotid sinus pressures held at 50 mmHg in both young (1 yr) and old animals (11 yr). In response to graded volume expansion (VE) with 3% dextran (0 to 30 ml/kg iv), the gain of cardiopulmonary baroreflex control of RSNA was significantly lower in the old (5.1 +/- 3%/mmHg) compared with the young (13.4 +/- 3%/mmHg) animals. There were no significant differences in systemic vascular compliance or left ventricular mass index between the two groups. The gain of the carotid sinus baroreflex inhibition of RSNA was significantly attenuated by VE in the young group but was not affected in the old group. Bilateral vagotomy (VX) resulted in a 182 +/- 74% increase in RSNA in the young (P less than 0.05), but VX did not significantly increase RSNA in the old (12 +/- 17%). After VX, the carotid sinus baroreflex gain markedly increased by nearly eightfold in the young group (P less than 0.05) but was not altered in the old dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise training attenuates baroreflex regulation of nerve activity in rabbits.

Baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) during changes in arterial pressure were examined in conscious rabbits before and after 8 wk of treadmill endurance exercise training. Exercise-induced bradycardia (decreased HR at rest and at identical workloads) was used to document a cardiovascular training effect. At 29.4 m/min, 20% grade, posttraining HR was significantly lower than pretraining values (295 +/- 6 beats/min vs. 361 +/- 8 beats/min, P less than 0.05). Rabbits were instrumented with an occluder around the inferior vena cava (IVCO), arterial and venous catheters, and recording electrodes around renal sympathetic nerves. Baroreflex-mediated changes in HR and RSNA to a 25-mmHg decrease and increase in mean arterial pressure (MAP) were obtained by inflating the IVCO or progressive infusion of phenylephrine, respectively. After training, the range (maximum response minus minimum response) of baroreflex control of RSNA and HR was significantly attenuated (209 +/- 12 vs. 413 +/- 14% and 123 +/- 16 vs. 162 +/- 8 beats/min). In addition, the slope of baroreflex control of HR and RSNA was significantly attenuated after training (4.17 +/- 0.35 vs. 8.32 +/- 0.23%/mmHg and 2.57 +/- 0.4 vs. 4.14 +/- 0.4 beats.min-1.mmHg-1). These data demonstrate that endurance exercise training significantly attenuated baroreflex control of HR and RSNA in conscious rabbits.

PGI2 attenuates baroreflex control of renal nerve activity by a vagal mechanism.

The present study was undertaken to determine whether left circumflex coronary artery (ic) administration of prostacyclin (PGI2) caused an inhibition of the baroreflex control of renal sympathetic nerve activity (RSNA). RSNA was recorded in 12 dogs. Baroreflex sensitivity of RSNA was assessed by infusion of either sodium nitroprusside or phenylephrine and by determining the slope of the mean arterial pressure-RSNA relationship. During nitroprusside infusion, intracoronary PGI2 depressed the baroreflex sensitivity by nearly 90% compared with intracoronary tris(hydroxymethyl)aminomethane (Tris) (P less than 0.002). In addition, the peak increase in RSNA during nitroprusside infusion was significantly inhibited during intracoronary PGI2 (57.9 +/- 6.4 vs. 21.2 +/- 3.0 spikes/s, P less than 0.05). There was no significant difference in the inhibition of RSNA during phenylephrine infusion when intracoronary PGI2 was compared with Tris. Both bilateral vagotomy and pericoronary lidocaine blocked the inhibitory effects of PGI2 on the baroreflex increase in RSNA. It is concluded from these data that exogenously administered PGI2 stimulates or sensitizes afferent endings within the supply of the left circumflex coronary artery to inhibit the baroreflex control of RSNA during evoked hypotension. These afferents traverse vagal pathways via the pericoronary nerves. The role of endogenous prostaglandins in modulation of baroreflex function via a cardiac reflex remains to be elucidated.