Christian Barrès

The arterial baroreceptor reflex of the rat exhibits positive feedback properties at the frequency of mayer waves.

1 Modelling studies have led to the proposal that Mayer waves (∼0.4 Hz in rats) could result from a resonance phenomenon in a feedback control loop. In this study, we investigated the presence of a resonance frequency in the arterial baroreceptor reflex loop, i.e. a particular frequency at which arterial pressure feeds back positively to the baroreceptors. 2 Frequency responses of mean arterial pressure (MAP) to aortic depressor nerve (ADN) stimulation were studied in fifteen urethane anaesthetized, ventilated rats with cardiac autonomic blockade. The ADN was stimulated using rectangular trains of impulses (2 ms, 100 Hz) delivered at frequencies ranging from 0.1 to 1 Hz. Phase angles between impulses and MAP were calculated using cross‐spectral analysis based on a fast Fourier transform algorithm. 3 Rhythmic ADN stimulation induced regular MAP oscillations at the expected frequencies that were attenuated by α‐adrenoceptor blockade and abolished after ganglionic blockade. The relationship between impulse and MAP oscillations was characterized by a strong coherence and a positive phase shift at low frequencies, indicating that impulses led MAP with respect to the out‐of‐phase pattern. Deviation of the phase from the out‐of‐phase behaviour was mainly due to the presence of a fixed time delay (∼0.8 s) between ADN stimuli and MAP changes. Phase angles fell to zero at 0.42 ± 0.02 Hz. 4 In rats, the arterial baroreceptor reflex exhibits a resonance frequency close to the frequency of spontaneously occurring Mayer waves. The reflex therefore seems the most likely origin for the Mayer waves.

Hemodynamic analysis of arterial pressure oscillations in conscious rats

This study examined the contribution of rhythmic fluctuations of regional blood flow and vascular conductance to the genesis of low- (LF, 0.27-0.74 Hz) and high- (HF, 0.76-5 Hz) frequency oscillations of arterial pressure. In conscious 15-week-old male intact (n = 11), guanethidine-sympathectomized (n = 8) and chronically sinoaortic denervated (n = 7) rats, arterial pressure and regional blood flow velocities (pulsed Doppler probes) were simultaneously recorded. Indices of subdiaphragmatic aortic, hindquarters and superior mesenteric conductances were calculated on a beat-to-beat basis over a 60-min period. Spectral power was calculated in the LF and HF bands using a fast Fourier transform algorithm. Transfer function analysis was also performed to calculate coherence and phase between arterial pressure and regional flows and conductances. In the LF band, spectral power of arterial pressure was decreased by approx. 85% in sympathectomized and approx. 54% in sinoaortic denervated rats. In the HF band, spectral power did not differ between the groups. In the three groups of rats, relations between arterial pressure and blood flow were characterized by a significant coherence in the HF band with little or no phase delay (synchronous oscillations). Relations between arterial pressure and vascular conductance were characterized in intact rats by a significant coherence in the LF band and a phase delay tending to pi radians (opposite oscillations), whereas in both sympathectomized and sinoaortic denervated rats, coherence did not reach significance. It is concluded that LF oscillations of arterial pressure are mostly secondary to rhythmic fluctuations in the vasomotor sympathetic tone in several regional circulations. Part of these oscillations originate from the synchronizing influence of the baroreceptor reflex. The study also suggests that the respiratory (HF) oscillations of arterial pressure involve fluctuations in cardiac output of purely mechanical origin.

ARTERIAL BAROREFLEX CONTROL OF HEART PERIOD IS NOT RELATED TO BLOOD PRESSURE VARIABILITY IN CONSCIOUS HYPERTENSIVE AND NORMOTENSIVE RATS

1. The short‐term (within 30 min periods) and the long‐term (among 30 min periods) variabilities, expressed as variation coefficients, of blood pressure (BP) and heart period (HP) were studied using a computer analysis of BP recordings in freely moving genetically hypertensive (LH), normotensive (LN) and low BP (LL) rats of Lyon strains at ages 5, 9, 21 and 40 weeks. The baroreflex control of HP was estimated with the slope of the linear relationship between systolic BP (SBP) and HP (SBP‐HP slope) computed after phenylephrine and nitroglycerin injections.

Linear modelling analysis of baroreflex control of arterial pressure variability in rats

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.

Renal Blood Flow Dynamics and Arterial Pressure Lability in the Conscious Rat

It is not known whether renal blood flow (RBF) is still autoregulated when the kidney is exposed to large transient blood pressure (BP) fluctuations such as those occurring spontaneously in conscious sinoaortic baroreceptor-denervated (SAD) rats. In this study, BP and RBF were simultaneously recorded in 8 SAD rats (2 weeks before study) and 8 baroreceptor-intact rats during ≈3 hours of spontaneous activity. The kidney used for RBF recordings was denervated to prevent the interference of changes in renal sympathetic tone with autoregulatory mechanisms. In intact rats, RBF variability (coefficient of variation 9.1±0.8%) was larger (P <0.02) than BP variability (5.9±0.2%). This was mainly because of slow changes in RBF that were unrelated to BP and also to a prominent oscillation of RBF of ≈0.25-Hz frequency. Autoregulatory patterns were identified at frequencies <0.1 Hz and provided a modest attenuation of BP fluctuations. In SAD rats, RBF variability (12.4±1.6%) was lower (P <0.02) than BP variability (18.2±1.1%). Autoregulation powerfully attenuated BP changes <0.1 Hz (normalized transfer gain 0.21±0.02 in the 0.0015- to 0.01-Hz frequency range) but at the expense of an oscillation located at ≈0.05 Hz that possibly reflected the operation of the tubuloglomerular feedback. Large transient hypertensive episodes were not translated into RBF changes in SAD rats. We conclude that autoregulatory mechanisms have an ample capacity to protect the kidney against spontaneous BP fluctuations in the conscious rat. This capacity is not fully used under normal conditions of low BP variability.

High blood pressure and metabolic disorders are associated in the Lyon hypertensive rat.

Objective: A large population of F2 rats, obtained from a cross between male Lyon hypertensive (LH) rats and female Lyon normotensive (LN) rats, was studied in order to assess the relationship between increased body weight, hyperlipidaemia and high blood pressure which characterize LH rats. Methods: Mean arterial pressure (MAP) was recorded in male, conscious, freely moving LH, LN, F1 and F2 rats aged 30 weeks. Plasma total cholesterol, high-density lipoprotein-, low-density lipoprotein- and very low-density lipoprotein-cholesterol, phospholipids, triglycerides, insulin and glucose were measured. Results: In the F2 cohort it was observed that high MAP was a recessive trait that depends on several genes and was unrelated to body weight. The left ventricular weight, corrected for tibia length, was correlated with MAP. Plasma total and high-density lipoprotein-cholesterol and phospholipids concentrations were lower in the F1 rats than in the LN rats, suggesting an overdominance of the LN alleles. In the F2 rats MAP was related to total, high-density lipoprotein- and low-density lipoprotein-cholesterol. Plasma triglycerides, insulin and the insulin: glucose ratio, which were higher in the LH rats than in the LN rats, were also correlated with MAP in the F2 cohort. Using stepwise multiple regression analysis, MAP remained correlated with plasma total cholesterol, insulin and the insulin: glucose ratio, but not with triglycerides. Conclusions: Hypertension in LH rats is a recessive trait that is independent of body weight. In addition, the cosegregation of blood pressure with plasma cholesterol and, to a lesser degree, with insulin levels, which was observed in the present study provides the first direct evidence that these phenotypes are associated and are not due simply to genetic drift in the Lyon model.

Steady-State and Dynamic Responses of Renal Sympathetic Nerve Activity to Air-Jet Stress in Sinoaortic Denervated Rats

Abstract—This study examined the role of arterial baroreceptors in mediating the relationship between changes in the mean level and the amplitude of slow oscillations of renal sympathetic nerve activity (RSNA) during environmental stress. In 7 sham-operated (control) and 7 chronically (2 weeks before study) sinoaortic baroreceptor denervated (SAD) conscious rats, arterial pressure (AP) and RSNA were simultaneously recorded during two 15-minute periods, before and during the application of a mild environmental stressor (jet of air). Air-jet stress induced a similar degree of sympathoexcitation in both groups of rats. During stress in control rats, AP and RSNA spectral power in the mid-frequency (MF) range (0.27 to 0.74 Hz) increased, mainly as a consequence of an amplification of strongly coherent oscillations of ≈0.4 Hz frequency. In SAD rats, MF fluctuations of AP and RSNA were reduced but not abolished before stress, tended to increase during stress, and were linearly related under both experimental conditions. However, in the MF range, there was no well-defined oscillation at any specific frequency. At the peak coherence frequency (≈0.4 Hz), the gain of the transfer function from RSNA to AP did not change during stress in control rats and was similar to that measured in SAD rats, indicating that it mainly reflected the properties of the feedforward effect of RSNA on AP (ie, vascular reactivity). In summary, the parallelism between stress-induced changes in the mean level of RSNA and the amplitude of slow RSNA oscillations requires the functional integrity of the baroreceptor reflex, which is consistent with the hypothesis that slow AP and RSNA rhythms are resonant oscillations within the baroreceptor reflex loop.

Frequency response of renal sympathetic nervous activity to aortic depressor nerve stimulation in the anaesthetized rat

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 ∼0.15 Hz), an overdamped second‐order low‐pass filter (natural frequency ∼1 Hz) and a fixed time delay (∼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).

Short-term haemodynamic variability in the conscious areflexic rat

1 Similtaneous measurements of arterial pressure and cardiac output (n= 8), mesenteric blood flow (n= 7) or hindquarters (n= 8) blood flow were performed during 1 h periods in conscious rats, before and after acute pharmacological blockade of the autonomic, renin‐angiotensin and vasopressin systems. In the latter condition (areflexic state), arterial pressure was maintained with a continuous infusion of noradrenaline. 2 In the areflexic state, spontaneous fluctuations in arterial pressure were markedly exaggerated, especially depressor episodes. At the onset of these falls in arterial pressure, there was an abrupt and transient decrease in stroke volume and cardiac output. Systemic vasodilatation then developed while cardiac output returned to normal. Regional vasodilatations were also delayed from the onset of the falls in arterial pressure and were usually large enough to maintain blood flow. 3 Both time and frequency domain analyses confirmed that changes in systemic and regional vascular conductances lagged by about 1 s behind arterial pressure changes. 4 These results indicate that, in the absence of neurohumoral influences, autoregulatory‐like mechanisms become dominant in the control of systemic and regional circulations and contribute to exaggeration of the spontaneous short‐term variability of arterial pressure.

Baroreceptor modulation of regional haemodynamic responses to acute stress in rat

We examined the effects of chronic sinoaortic denervation (SAD) on regional haemodynamic responses to acute environmental stress in rats. In conscious male intact (n = 12) and SAD (2 weeks before study, n = 7) rats, arterial pressure and blood flow velocities (pulsed Doppler probes) in the subdiaphragmatic aorta, superior mesenteric artery and distal aorta (hindquarters) were simultaneously recorded. In response to air jet stress, intact rats showed modest increases in arterial pressure that were accompanied by vasoconstriction in the mesentery and vasodilatation in the hindquarters. These regional haemodynamic changes were almost balanced, as indicated by the lack of change in the subdiaphragmatic aortic conductance. SAD markedly enhanced the pressor and mesenteric vasoconstrictor responses and blunted the hindquarters vasodilatation. After acute beta-adrenoceptor blockade with propranolol, the stress-induced hindquarters vasodilatation was strongly reduced in the intact rats and was reversed into vasoconstriction in the SAD rats. These results point to an opposing interaction between centrally-induced sympathoexcitation and arterial baroreceptor reflex activation during stress. This probably favours the hyperaemic response in the skeletal muscles at a lower metabolic cost.