Central chemoreflex activation induces sympatho-excitation without altering static or dynamic baroreflex function in normal rats

Figures

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  Figure 1. (A) Representative time series of sympathetic nerve activity (SNA) and arterial pressure (AP) under central chemoreflex activation from one rat. Central chemoreflex activation was induced by inhalation of 3 and 5% CO 2 gas mixture. Changes in sympathetic nerve activity (B) and mean arterial pressure (C) under central chemoreflex activation induced by inhalation of a gas mixture containing 3% and 5% CO 2. The data were obtained from five rats. Both the PaCO 2–SNA (SNA = 2.60 × PaCO2 + 0.65, r 2 = 0.9994) and PaCO2–mean AP relationships (AP = 1.77 × PaCO 2 + 25.77, r 2 = 0.9995) show linearity. Changes in PaCO 2 were shown in Table 1. CSP, carotid sinus pressure; SNA, sympathetic nerve activity; SNA with LPF, sympathetic nerve activity with low‐pass filter (cutoff frequency; 0.5 Hz); AP, arterial pressure; MAP, mean arterial pressure; PaCO 2, partial pressure of carbon dioxide in arterial blood. Data are expressed as mean ± SD (n = 5). *P < 0.05 versus baseline. † P < 0.05 versus 3% CO 2.

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  Figure 2. Typical time series of carotid sinus pressure (CSP), sympathetic nerve activity (SNA) and arterial pressure (AP) at baseline and after under central chemoreflex (CR) activation from one rat in protocol 2. Data were resampled at 50 Hz. SNA and AP decreased in response to stepwise increment in CSP both at baseline and under central chemoreflex activation. Central chemoreflex activation further increased SNA and AP at each level of CSP. CO 2, concentration of CO 2 (%) in gas mixture measured by gas analyzer; CSP, carotid sinus pressure; SNA with LPF, sympathetic nerve activity with low‐pass filter (cutoff frequency; 0.5 Hz); AP, arterial pressure.

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  Figure 3. Mean baroreflex mechanoneural, neuromechanical and total arcs at baseline (dashed line with open circles) and under central chemoreflex activation (solid line with closed circles) averaged over five rats in protocol 2. Central chemoreflex activation shifted the mechanoneural arc to higher SNA, but did not change the neuromechanical arc. SNA, sympathetic nerve activity; CSP, carotid sinus pressure; AP, arterial pressure. Data are expressed as mean ± SEM.

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  Figure 4. Representative time series of sympathetic nerve activity (SNA) and arterial pressure (AP) under carotid sinus pressure (CSP) perturbation from one rat in protocol 3. Data were resampled at 50 Hz. CSP was perturbed according to binary white noise sequences. Inhalation of 3% CO 2 gas mixture increased PaCO 2 from 37 mmHg to 48 mmHg in this rat. CSP perturbation changed SNA and AP. Under central chemoreflex (CR) activation, SNA and AP increased at each CSP level. CSP, carotid sinus pressure; SNA, sympathetic nerve activity; AP, arterial pressure.

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  Figure 5. Transfer functions (H) of mechanoneural, neuromechanical and total arcs obtained at baseline (dashed line) and under central chemoreflex (CR) activation (solid line). Mean gain, phase (radian), coherence and step response averaged over five rats are shown. The error band of each graph is not shown for visibility. The gain of transfer function in mechanoneural arc was normalized by the mean dynamic gain below 0.03 Hz at baseline.

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  Figure 6. Baroreflex equilibrium diagram and the scheme of interaction between central chemoreflex activation and baroreflex. The dashed and solid lines indicate two subsystems of baroreflex function at baseline and under central chemoreflex activation, respectively. The operating point at baseline (a) is determined from the intersection of the mechanoneural and neuromechanical arcs. The absence of baroreflex feedback loop allows increase in AP to 146.3 mmHg and SNA to 114.8% (b). Since baroreflex forms a negative feedback loop, the operating point under central chemoreflex activation shifts to (c) at AP of 127.0 mmHg and SNA of 94.5%.

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  Figure 7. The effect of central chemoreflex activation on AP control system of the baroreflex. (A) The baroreflex mechanoneural arc regulates SNA by the product of gain (G) and difference between a given AP and command pressure. The baroreflex neuromechanical arc changes AP by SNA. Sato et al. (1999) proposed this framework. (B) The command pressure, in functional term, is the pressure that nullifies SNA on the tangential line drawn through the operating point of mechanoneural arc. It characterizes the mechanoneural arc around the operating point. The pressure axis intercept of linearized mechanoneural arc represents the command pressure. (C) Central chemoreflex (CR) activation increases the baroreflex command pressure (table), but does not change the dynamic characteristics of the baroreflex system. Thus, CR activation induces sympathetic‐excitation without compromising the pressure buffering function of the baroreflex.