The role of arterial baroreceptors in controlling arterial pressure (AP) variability through changes in sympathetic nerve activity was examined in conscious rats. AP and renal sympathetic nerve activity (RSNA) were measured continuously during 1-h periods in freely behaving rats that had been subjected to sinoaortic baroreceptor denervation (SAD) or a sham operation 2 wk before study (n = 10 in each group). Fast Fourier transform analysis revealed that chronic SAD did not alter high-frequency (0.75-5 Hz) respiratory-related oscillations of mean AP (MAP) and RSNA, decreased by approximately 50% spectral power of both variables in the midfrequency band (MF, 0.27-0.74 Hz) containing the so-called Mayer waves, and induced an eightfold increase in MAP power without altering RSNA power in the low-frequency band (0.005-0.27 Hz). In both groups of rats, coherence between RSNA and MAP was maximal in the MF band and was usually weak at lower frequencies. In SAD rats, the transfer function from RSNA to MAP showed the characteristics of a second-order low-pass filter containing a fixed time delay ( approximately 0.5 s). These results indicate that arterial baroreceptors are not involved in production of respiratory-related oscillations of RSNA but play a major role in the genesis of synchronous oscillations of MAP and RSNA at the frequency of Mayer waves. The weak coupling between slow fluctuations of RSNA and MAP in sham-operated and SAD rats points to the interference of noise sources unrelated to RSNA affecting MAP and of noise sources unrelated to MAP affecting RSNA.

Adult skeletal muscle is capable of complete regeneration after an acute injury. The main parameter studied to assess muscle regeneration efficacy is the cross-sectional area (CSA) of the myofibers as myofiber size correlates with muscle force. CSA analysis can be time-consuming and may trigger variability in the results when performed manually. This is why programs were developed to completely automate the analysis of the CSA, such as SMASH, MyoVision, or MuscleJ softwares. Although these softwares are efficient to measure CSA on normal or hypertrophic/atrophic muscle, they fail to efficiently measure CSA on regenerating muscles. We developed Open-CSAM, an ImageJ macro, to perform a high throughput semi-automated analysis of CSA on skeletal muscle from various experimental conditions. The macro allows the experimenter to adjust the analysis and correct the mistakes done by the automation, which is not possible with fully automated programs. We showed that Open-CSAM was more accurate to measure CSA in regenerating and dystrophic muscles as compared with SMASH, MyoVision, and MuscleJ softwares and that the inter-experimenter variability was negligible. We also showed that, to obtain a representative CSA measurement, it was necessary to analyze the whole muscle section and not randomly selected pictures, a process that was easily and accurately be performed using Open-CSAM. To conclude, we show here an easy and experimenter-controlled tool to measure CSA in muscles from any experimental condition, including regenerating muscle.Electronic supplementary materialThe online version of this article (10.1186/s13395-018-0186-6) contains supplementary material, which is available to authorized users.

The objective of the present study was to examine whether a simple linear feedback model of arterial pressure (AP) control by the sympathetic nervous system would be able to reproduce the characteristic features of normal AP variability by using AP and renal sympathetic nerve activity (RSNA) data collected in conscious sinoaortic baroreceptor denervated (SAD) rats. As compared with baroreceptor-intact rats (n = 8), SAD rats (n = 10) had increased spectral power (+ 680%) of AP in the low frequency range (LF, 0.0003-0.14 Hz) and reduced power (−19%) in the mid-frequency range (MF, 0.14-0.8 Hz) containing Mayer waves. In individual SAD rats, RSNA data were translated into 'sympathetic' AP time series by using the RSNA-AP transfer function that had been previously characterized in anaesthetized rats. AP 'perturbation' time series were then calculated by subtracting 'sympathetic' from actual AP time series. Actual RSNA and AP 'perturbation' time series were introduced in a reflex loop that was closed by using the previously identified baroreflex transfer function (from baroreceptor afferent activity to RSNA). By progressively increasing the open-loop static gain, it was possible to compute virtual AP power spectra that increasingly deviated from their progenitor spectra, with spectral power decreasing in the LF range (as a result of baroreflex buffering of haemodynamic perturbations), and increasing in the MF band (as a result of increasing transients at the resonance frequency of the loop). The most accurate reproduction of actual AP and RSNA spectra observed in baroreceptor-intact rats was obtained at 20-30% of the baroreflex critical gain (open-loop static gain resulting in self-sustained oscillations at the resonance frequency). In conclusion, while the gain of the sympathetic component of the arterial baroreceptor reflex largely determines its ability to provide an efficient correction of slow haemodynamic perturbations, this is achieved at the cost of increasing transients at higher frequencies (Mayer waves). However, the system remains fundamentally stable. In freely moving rats, sympathetic nerve activity (SNA) and arterial pressure (AP) show parallel increases during the performance of common behaviours (Miki et al. 2003). In chronically sympathectomized rats, the same behaviours are accompanied by falls rather than increases in AP (Julien et al. 1990;Ferrari et al. 1996), which indicates that behaviourally coupled changes in SNA are effectively responsible for AP changes in the intact animal. From these simple observations, a tight coupling between AP and SNA variabilities would be expected. However, this is not the case. Using frequency-domain approaches, it was found that AP and SNA are correlated in a narrow frequency band (0.4 ± 0.2 Hz in rats). This band, usually referred to as the mid-frequency band, contains the so-called AP Mayer waves (Brown et al. 1994). The correlation (or coherence) between AP and SNA at lower frequencies, where the bulk of AP variability is concentrated, is either weak or incon...

The present study examined the effects of baroreceptor loading and unloading on the various rhythms present in the renal sympathetic nerve activity (RSNA) of 10 conscious rats. Short-lasting (4-5 min), steady-state decreases (from -10 to -40 mmHg) and increases (from 5 to 30 mmHg) in arterial pressure (AP) were induced by the intravenous infusion of sodium nitroprusside and phenylephrine, respectively. The relationship between changes in AP level and RSNA total power (fast Fourier transform analysis; 0-25 Hz) was characterized by an inverse sigmoid function. Basal AP was located 6.3 mmHg above AP at the midrange of the curve, that is, near the lower plateau. Sigmoid relationships were also observed for spectral powers in the low (LF, 0.030-0.244 Hz), respiratory (0.79-2.5 Hz) and high-frequency (HF, 2.5-25 Hz) bands. In contrast, in the MF band (0.27-0.76 Hz) containing oscillations associated with Mayer waves, the AP-RSNA power relationship showed a bell curve shape with a maximum at 21 mmHg below basal AP. Similarly, changes in RSNA power at the frequency of the heart beat were well characterized by a bell curve reaching a maximum at 22 mmHg below basal AP. Under baseline conditions, LF, MF, respiratory and HF powers contributed approximately 3, 10, 18, and 69% of the total RSNA power, respectively. The pulse-synchronous oscillation of RSNA accounted for only 11 +/- 1% of HF power. The contribution of HF power to total power did not change consistently with AP changes. Therefore, most of the baroreflex-induced changes in RSNA are mediated by changes in the amplitude of fast, irregular fluctuations.

1. The contribution of central baroreceptor reflex pathways to the dynamic regulation of sympathetic nervous activity (SNA) has not been properly examined thus far. The aim of this study was to characterize the transfer function of the central arc of the baroreceptor reflex (from baroreceptor afferent activity to SNA) over a wide range of frequencies. 2. In nine baroreceptor-intact and six sino-aortic baroreceptor-denervated rats anaesthetized with urethane, the renal SNA was recorded while applying sinusoidal stimulation to the aortic depressor nerve at 26 discrete frequencies ranging from 0.03 to 20 Hz. At each modulation frequency, cross-power spectrum analysis using a fast Fourier transform algorithm was performed between the stimulation and renal SNA, which provided the transfer function of the central arc. 3. In both baroreceptor intact and denervated rats, the transfer gain increased by a factor of about three between 0.03 and 1 Hz. At higher frequencies, the gain decreased but remained above the static gain of the system up to 12 Hz. There was a slight phase lead up to 0.4 Hz, then a continuously increasing phase lag. A three-element linear model satisfactorily described the experimental transfer function. The model combined a derivative gain (corner frequency approximately 0.15 Hz), an overdamped second-order low-pass filter (natural frequency approximately 1 Hz) and a fixed time delay (approximately 100 ms). 4. These results indicate that the central arc of the baroreceptor reflex shows derivative properties that are essential for compensating the filtering of fast oscillations of baroreceptor afferent activity and thus for the generation of fast oscillations of renal SNA (e.g. those related to the cardiac cycle).

The present study examined whether the gain of the transfer function relating cardiac-related rhythm of renal sympathetic nerve activity (RSNA) to arterial pressure (AP) pulse might serve as a spontaneous index of sympathetic baroreflex sensitivity (BRS). AP and RSNA were simultaneously recorded in conscious rats, either baroreceptor-intact (control, n = 11) or with partial denervation of baroreflex afferents [aortic baroreceptor denervated (ABD; n = 10)] during 1-h periods of spontaneous activity. Transfer gain was calculated over 58 adjacent 61.4-s periods (segmented into 10.2-s periods). Coherence between AP and RSNA was statistically (P < 0.05) significant in 90 +/- 3% and 56 +/- 10% of cases in control and ABD rats, respectively. Transfer gain was higher (P = 0.0049) in control [2.39 +/- 0.13 normalized units (NU)/mmHg] than in ABD (1.48 +/- 0.22 NU/mmHg) rats. In the pooled study sample, transfer gain correlated with sympathetic BRS estimated by the vasoactive drug injection technique (R = 0.75; P < 0.0001) and was inversely related to both time- (standard deviation; R = -0.74; P = 0.0001) and frequency-domain [total spectral power (0.00028-2.5 Hz); R = -0.82; P < 0.0001] indices of AP variability. In control rats, transfer gain exhibited large fluctuations (coefficient of variation: 34 +/- 3%) that were not consistently related to changes in the mean level of AP, heart rate, or RSNA. In conclusion, the transfer function method provides a continuous, functionally relevant index of sympathetic BRS and reveals that the latter fluctuates widely over time.

Pires, Silene L. S., Claude Julien, Bruno Chapuis, Jean Sassard, and Christian Barrè s. Spontaneous renal blood flow autoregulation curves in conscious sinoaortic baroreceptor-denervated rats. Am J Physiol Renal Physiol 282: F51-F58, 2002. First published August 8, 2001 10.1152/ajprenal.00186.2001.-These experiments examined whether the conscious sinoaortic baroreceptor-denervated (SAD) rat, owing to its high spontaneous arterial pressure (AP) variability, might represent a model for renal blood flow (RBF) autoregulation studies. In eight SAD and six baroreceptor-intact rats, AP and RBF were recorded (1-h periods) before and after furosemide (10 mg/kg followed by 10 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 iv) administration. In control conditions, AP variability was markedly enhanced in SAD rats (coefficient of variation: 16.0 Ϯ 1.2 vs. 5.4 Ϯ 0.5% in intact rats), whereas RBF variability was only slightly increased (8.7 Ϯ 0.6 vs. 6.1 Ϯ 0.5% in intact rats), suggesting buffering by autoregulatory mechanisms. In SAD rats, but not in intact rats, the AP-RBF relationships could be modeled with a four-parameter sigmoid Weibull equation (r 2 ϭ 0.24 Ϯ 0.07, 3,600 data pairs/rat), allowing for estimation of an autoregulatory plateau (10.1 Ϯ 0.7 ml/min) and a lower limit of RBF autoregulation (PLL ϭ 93 Ϯ 6 mmHg, defined as AP at RBF 5% below the plateau). After furosemide treatment, autoregulation curves (r 2 ϭ 0.49 Ϯ 0.07) in SAD rats were shifted downward (plateau ϭ 8.6 Ϯ 0.8 ml/min) and rightward (PLL ϭ 102 Ϯ 5 mmHg). In five of six intact rats, PLL became measurable (104 Ϯ 1 mmHg), albeit with limited accuracy (r 2 ϭ 0.09 Ϯ 0.03). In conclusion, the conscious SAD rat offers the possibility of describing RBF autoregulation curves under dynamic, unforced conditions. The tubuloglomerular feedback and myogenic mechanisms cooperate in setting PLL and thus in stabilizing RBF during spontaneous depressor episodes.arterial pressure variability; furosemide; modeling AUTOREGULATION OF TOTAL RENAL blood flow (RBF) is usually explored by measuring RBF responses to externally induced stepwise reductions of arterial pressure (AP) in both anesthetized (6,8,11,13,17,21,22) and conscious (2,4,16,18,(24)(25)(26) animals. Steady-state levels of RBF are plotted as a function of AP, which allows the drawing of autoregulation curves from which the plateau and lower pressure limit of RBF autoregulation (P LL ) are estimated. It is not known whether such information can be gained under spontaneous unforced conditions, i.e., using RBF responses to naturally occurring AP fluctuations.The conscious sinoaortic baroreceptor-denervated (SAD) rat is a well-recognized model of exaggerated AP variability, which is characterized by the spontaneous occurrence of pressor and depressor episodes of occasionally large amplitude (3,28). Recently, we have investigated in conscious SAD rats the relationships between AP variability and RBF variability (20). Although AP variability was markedly increased, RBF variability was only slightly increased, suggesting a powerful participa...

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