This systematic review and meta-analysis with accompanying summary of non-parametric data shows elevated maternal circulating TNF-α, IL-6, and IL-10 levels in preeclampsia.

Abstract-Increasing evidence suggests elevated sympathetic outflow may be important in the genesis of hypertension. It is thought that peripheral angiotensin II, in addition to its pressor actions, may act centrally to increase sympathetic nerve activity (SNA). Without direct long-term recordings of SNA, testing the involvement of neural mechanisms in angiotensin II-induced increases in arterial pressure is difficult. Using a novel telemetry-based implantable amplifier, we made continuous recordings of renal SNA (RSNA) before, during, and after 1 week of angiotensin II-based hypertension in rabbits living in their home cages. Angiotensin II infusion (50 ng · kg Ϫ1 · min Ϫ1) caused a sustained increase in arterial pressure (18Ϯ3 mm Hg). There was a sustained decrease in RSNA from 18Ϯ2 normalized units (n.u.) before angiotensin II to 8Ϯ2 n.u. on day 2 and 9Ϯ2 n.u. on day 7 of the angiotensin II infusion (PϽ0.01) before recovering to 17Ϯ2 n.u. after ceasing angiotensin II. Analysis of the baroreflex response showed that although angiotensin II-induced hypertension led to resetting of the relationship between mean arterial pressure (MAP) and heart rate, there was no evidence of resetting of the MAP-RSNA relationship. We propose that the lack of resetting of the MAP-RSNA curve, with the resting point lying near the lower plateau, suggests the sustained decrease in RSNA during angiotensin II is baroreflex mediated. These results suggest that baroreflex control of RSNA and thus renal function is likely to play a significant role in the control of arterial pressure not only in the short term but also in the long term. Key Words: rabbits Ⅲ telemetry Ⅲ angiotensin II Ⅲ baroreflex Ⅲ sympathetic nerve activity S everal previous studies indicate that the sympathetic nervous system plays a critical role in the development of hypertension. In young or borderline hypertensive subjects, it is clear that plasma catecholamines are elevated 1-3 and muscle sympathetic activity is increased. 4,5 Importantly, it seems that rather than generalized overactivity of the sympathetic nervous system occurring, it is specifically increased renal sympathetic nerve activity (RSNA), resulting in diminished renal function, that is important. In young borderline hypertensive patients, noradrenaline spillover from the kidney is particularly elevated. 6,7 Animal models have identified that the onset of hypertension may be delayed or the magnitude of the arterial pressure elevation may be reduced by chronic renal denervation. 8 -12 Other studies have used longterm infusions of norepinephrine directly into the renal artery to mimic increased RSNA and observed the retention of sodium and water and sustained increases in arterial pressure. [13][14][15] These results have been interpreted to suggest that an integral relationship exists between functional sympathetic outflow to the kidneys and the development of hypertension.Although much progress has been made in recent years on the central nervous system pathways involved in regulating sympathetic acti...

Since the first recording of sympathetic nerve activity (SNA) early last century, numerous methods for presentation of the resulting data have developed. In this paper, we discuss the common ways of describing SNA and their application to chronic recordings. Suggestions on assessing the quality of SNA are made, including the use of arterial pressure wave-triggered averages and nasopharyngeal stimuli. Calculation of the zero level of the SNA signal from recordings during ganglionic blockade, the average level between bursts and the minimum of arterial pressure wave-triggered averages are compared and shown to be equivalent. The use of normalization between zero and maximal SNA levels to allow comparison between groups is discussed. We recommend that measured microvolt levels of integrated SNA be presented (with the zero/noise level subtracted), along with burst amplitude and frequency information whenever possible. We propose that standardization of the quantifying/reporting of SNA will allow better comparison between disease models and between research groups and ultimately allow data to be more reflective of the human situation.

Abstract-Arterial baroreflexes are well established to provide the basis for short-term control of arterial pressure;however, their role in long-term pressure control is more controversial. We proposed that if the sustained decrease in renal sympathetic nerve activity (RSNA) we observed previously in response to angiotensin II-induced hypertension is baroreflex mediated, then the decrease in RSNA in response to angiotensin II would not occur in sinoaortic-denervated (SAD) animals. Arterial pressure and RSNA were recorded continuously via telemetry in sham and SAD rabbits living in their home cages before, during, and after a 7-day infusion of angiotensin II (50 ng ⅐ kg Ϫ1 ⅐ min Ϫ1). The arterial pressure responses in the 2 groups of rabbits were not significantly different (82Ϯ3 mm Hg sham versus 83Ϯ3 mm Hg SAD before angiotensin II infusion, and 101Ϯ6 mm Hg sham versus 100Ϯ4 mm Hg SAD day 6 of angiotensin II). In sham rabbits, there was a significant sustained decrease in RSNA (53Ϯ7% of baseline on day 2 and 65Ϯ7% on day 6 of the angiotensin II). On ceasing the angiotensin II, all variables recovered to baseline. In contrast, RSNA did not change in SAD rabbits with the angiotensin II infusion (RSNA was 98Ϯ8% of baseline on day 2 and 98Ϯ8% on day 6 of the angiotensin II infusion). These results support our hypothesis that the reduction in RSNA in response to a pressor dose of angiotensin II is dependent on an intact arterial baroreflex pathway. Key Words: baroreceptors Ⅲ denervation Ⅲ rabbits Ⅲ nervous system, sympathetic renal A rterial baroreflexes are well established to provide the basis for the short-term control of arterial pressure; however, it has generally been accepted that they do not regulate long-term pressure. 1 This concept is based on 3 main lines of evidence, the first being that arterial baroreceptors reset during sustained increases in arterial pressure. 2 Second, chronic sinoaortic denervation, while producing tremendous lability in arterial pressure, does not result in higher average 24-hour pressures. 3 Finally, it is thought that the reflex gain of the baroreceptor control system is not sufficiently strong to explain the long-term constancy of arterial pressure. 4 However, a number of recent experiments have renewed interest in the role of the baroreflex in long-term arterial pressure control and suggest that arterial baroreflexes may act chronically to suppress sympathetic nerve activity. Lohmeier et al 5 studied responses to 5 days of angiotensin II infusion in dogs using a split-bladder preparation combined with denervation of 1 kidney. During angiotensin II infusion, sodium excretion from the innervated kidney significantly increased compared with the denervated kidney, indicating a decrease in renal sympathetic nerve activity (RSNA). The sustained increase in sodium excretion from the innervated kidney was proposed to be mediated by a sustained baroreflex-mediated suppression of RSNA because after cardiopulmonary and sinoaortic denervation, the sodium excretion from the innervated kid...

Guild, Sarah-Jane, Paul C. Austin, Michael Navakatikyan, John V. Ringwood, and Simon C. Malpas. Dynamic relationship between sympathetic nerve activity and renal blood flow: a frequency domain approach. Am J Physiol Regulatory Integrative Comp Physiol 281: R206-R212, 2001.-Blood pressure displays an oscillation at 0.1 Hz in humans that is well established to be due to oscillations in sympathetic nerve activity (SNA). However, the mechanisms that control the strength or frequency of this oscillation are poorly understood. The aim of the present study was to define the dynamic relationship between SNA and the vasculature. The sympathetic nerves to the kidney were electrically stimulated in six pentobarbital-sodium anesthetized rabbits, and the renal blood flow response was recorded. A pseudo-random binary sequence (PRBS) was applied to the renal nerves, which contains equal spectral power at frequencies in the range of interest (Ͻ1 Hz). Transfer function analysis revealed a complex system composed of low-pass filter characteristics but also with regions of constant gain. A model was developed that accounted for this relationship composed of a 2 zero/4 pole transfer function. Although the position of the poles and zeros varied among animals, the model structure was consistent. We also found the time delay between the stimulus and the RBF responses to be consistent among animals (mean 672 Ϯ 22 ms). We propose that the identification of the precise relationship between SNA and renal blood flow (RBF) is a fundamental and necessary step toward understanding the interaction between SNA and other physiological mediators of RBF. modeling; pseudo-random binary sequence SYMPATHETIC NERVE ACTIVITY (SNA) has been proposed to play an important role in the regulation of renal blood flow (RBF) (12). Whereas much previous research has focused on how the mean level of SNA regulates the mean level of RBF in response to a range of afferent stimuli (10), there has been little consideration given to fact that SNA is a signal made up of multiple frequency bands, ranging from 10 to 0.1 Hz (9). Surprisingly little is known about how these frequency components impact on the renal vasculature. Mathematical models have been developed to describe the effect blood pressure has on RBF (4-6). These models have proven useful in understanding the dynamics of autoregulation and tubuloglomerular feedback; however, there is a paucity of information on the dynamics of the neural control of RBF. Information on how the various frequencies in SNA regulate RBF is likely to be valuable in understanding the origin of oscillations present in blood pressure (2) and in predicting how diseases or therapeutic treatments that alter SNA could affect the control of RBF and potentially blood pressure.Previous work by our lab has determined that the renal vasculature appears only able to follow frequencies in SNA below 0.7 Hz, with frequencies above this level producing steady vascular tone (11). The corresponding frequency response characteristics suggested that a ...

We tested for regional differences in perfusion responses, within the renal medulla and cortex, to renal nerve stimulation in pentobarbital sodium-anesthetized rabbits. Laser-Doppler flux (LDF) was monitored at various depths below the cortical surface (1–15 mm). Basal cortical LDF (1–3 mm, ∼200–450 U) was greater than medullary LDF (5–15 mm, ∼70–160 U), but there were no statistically significant differences in basal LDF within these regions. The background LDF signal during aortic occlusion was similar in the cortex (2 mm, 31 U) and outer medulla (7 mm, 31 U), but slightly greater in the inner medulla (12 mm, 44 U). During electrical stimulation of the renal nerves (0.5–8 Hz), cortical LDF and total renal blood flow were similarly progressively reduced with increasing stimulus frequency. Medullary LDF (measured between 5 and 15 mm) was overall less responsive than cortical LDF. For example, 4-Hz stimulation reduced inner medullary LDF (9 mm) by 19 ± 6% but reduced cortical LDF (1 mm) by 54 ± 11%. However, medullary LDF responses to nerve stimulation were similar at all depths measured. Our results indicate that while the vascular elements controlling medullary perfusion are less sensitive to the effects of electrical stimulation of the renal nerves than are those controlling cortical perfusion, sensitivity within these vascular territories appears to be relatively homogeneous.

AJ. The role of the neural sympathetic and parasympathetic systems in diurnal and sleep state-related cardiovascular rhythms in the late-gestation ovine fetus. Am J Physiol Regul Integr Comp Physiol 297: R998 -R1008, 2009. First published July 29, 2009 doi:10.1152/ajpregu.90979.2008.-The efferent mechanisms mediating the well-known diurnal cardiovascular rhythms in the lategestation fetus are only partially understood. In the present study, we evaluated the contribution of the parasympathetic and sympathetic nervous systems (SNS) to these rhythms. Chronically instrumented fetal sheep at a mean (SE) of 122 (1) days gestation (term is 147 days) underwent either chemical sympathectomy with 6-hydroxydopamine the day after surgery (n ϭ 8), vagotomy at surgery (n ϭ 8), or were sham controls (n ϭ 8). Fetal heart rate (HR), fetal HR variability (HRV), mean arterial blood pressure (MAP), carotid blood flow (CaBF), electrocorticogram (ECoG) activity, and nuchal activity were measured continuously for 24 h. Changes between sleep states were determined in a 6-h interval. Control fetal sheep showed consistent diurnal rhythms in fetal HR, HRV, MAP, and CaBF, with maximal activity in the evening, but not in nuchal activity. Sympathectomy was associated with a significant reduction of both fetal HR and HRV, while vagotomy was associated with a fall in fetal HRV (P Ͻ 0.05) but no change in HR. Despite this, most animals in the two intervention groups still showed diurnal rhythms for fetal HR, HRV, MAP, and CaBF, although peak HR may have been delayed in the sympathectomy group (mean 02:22 vs. 23:54 h in controls, P ϭ 0.06). There was no effect of either intervention on sleep state cycling, although state-related cardiovascular rhythms were significantly modulated. These data indicate that, neither the SNS nor vagal activity, in isolation at least, is essential for generating cardiovascular diurnal rhythms in the late-gestation fetus. fetal heart rate variability; diurnal rhythm; fetal sheep; sleep state; autonomic nervous system DESPITE THE COMMON USE OF heart rate (HR) and HR variability (HRV) for fetal surveillance, the underlying efferent mechanisms controlling these rhythms remain incompletely understood (29). Diurnal rhythms in fetal HR and HRV are well established in late gestation in the fetal human (44), nonhuman primates (39), and sheep (3,4,9,11,42). These circadian rhythms are thought to be entrained by maternal signals (28) and coordinated, in part, by signals from a fetal "biological clock" in the suprachiasmatic nucleus (SCN) (5,26,41), although other fetal tissues may be involved (37). A study in infants and children showed a circadian rhythm in HR and HRV and confirmed progressive maturation of the autonomic nervous system with age, suggesting the hypothesis that the sympathetic withdrawal associated with mature, organized sleep is largely responsible for those rhythms (24).The SCN neurons communicate with the superior cervical ganglion, whose sympathetic terminals then release norepinephrine in end organs in a...

We have explored the possibility that renal sympathetic nerve activity (RSNA) and vasomotor sympathetic nerve activity are differentially regulated. We measured sympathetic nerve activity (SNA) to the kidney and the hind limb vasculature in seven conscious rabbits 6 -8 days after the implantation of recording electrodes. Acute infusion of N G -nitro-Larginine methyl ester (L-NAME) (6 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 for 5 min) led to an increase in blood pressure (from 66 Ϯ 1 to 82 Ϯ 3 mmHg) and a decrease in heart rate (from 214 Ϯ 15 to 160 Ϯ 13 bpm). L-NAME administration caused a significantly greater decrease in RSNA than lumbar sympathetic nerve activity (LSNA) (to 68 Ϯ 14% vs. 84 Ϯ 4% of control values, respectively). Volume expansion (1.5 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 ) resulted in a significant decrease in RSNA to 66 Ϯ 7% of control levels but no change in LSNA (127 Ϯ 20%). There was no difference in the gain of the baroreflex curves between the LSNA and RSNA [maximum gain of Ϫ7.6 Ϯ 0.4 normalized units (nu)/ mmHg for LSNA vs. Ϫ7.9 Ϯ 0.75 nu/mmHg for RSNA]. A hypoxic stimulus (10% O2 and 3% CO2) led to identical increases in both RSNA and LSNA (195 Ϯ 40% and 158 Ϯ 21% of control values, respectively). Our results indicate tailored differential control of RSNA and LSNA in response to acute stimuli. sympathetic activity; blood pressure EARLY CONCEPTS OF AUTONOMIC control suggested a global uniform activation of sympathetic nerve activity (SNA) to all organs in response to a "fight or flight" stimulus (3). The general convention was to refer to SNA as if the same signal travels to all organs, but this has been replaced with a more organized model that emphasizes differential control of sympathetic outflow to functionally specific targets (4, 22). Sympathetic nerve activity appears to be elevated in hypertension (9, 10), and half of the increase can be accounted for by increased norepinephrine spillover solely from the heart and the kidney (7,8). The selective increase in cardiac and renal sympathetic nerve activity (RSNA) indicates the importance of studying the differential control of nerve activity to better understand the control of blood pressure. The majority of evidence supporting differential control of SNA has come from anesthetized experiments in which sympathetic outflow to different organs in response to stimuli, such as volume expansion and baroreceptor stimulation, were measured.Studies in anesthetized rabbits have shown that volume expansion leads to an inhibition of RSNA (32). This reduction in RSNA with volume expansion appears to be differentially regulated compared with SNA to other nonrenal organs. Although volume expansion is also accompanied by a decrease in lumbar SNA (LSNA), this decrease appears to be differentially regulated compared with the RSNA response (33), although it must be mentioned that the two nerve activities were recorded in two separate sets of animals. It is pertinent to note that both of these studies were conducted in anesthetized rabbits. Recent studies have indicated that anesthesia can...