Quantitative assessment of the central versus peripheral effect of intravenous clonidine using baroreflex equilibrium diagrams

Figures

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  Fig. 1. Time series of carotid sinus pressure (CSP), sympathetic nerve activity (SNA), arterial pressure (AP), and heart rate (HR) obtained in one rat. In the left panels, stepwise CSP changes were repeated and referred to as S1 to S6. One minute after the completion of S2, low-dose (2 μg/kg) clonidine was intravenously administered. One minute after the completion of S4, high-dose (5 μg/kg) clonidine was intravenously administered. The baroreflex response in S2 was treated as the control, whereas the responses in S4 and S6 were used to evaluate the effects of low-dose and high-dose clonidine, respectively. In the right panels, hexamethonium bromide (C6) was intravenously administered. CSP was servo-controlled to mimic instantaneous AP during the C6 protocol. The CSP and AP signals are virtually the same at this time resolution. SNA was depicted as a 10-Hz resampled signal (gray) and a 2-s moving averaged signal (black). AP and HR were depicted as 200-Hz resampled signals (gray) and 2-s moving averaged signals (black)

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  Fig. 2. Open-loop static characteristics of the total reflex arc (A), HR control (B), neural arc (C), and peripheral arc (D) together with their parameter values (E–H). CSP carotid sinus pressure, AP arterial pressure, HR heart rate, SNA sympathetic nerve activity, P1 response range, P2 slope coefficient; P3 midpoint input pressure, P4 lower asymptote of the fitted sigmoid curve. Labels C, L, H denote the data under control conditions, after low-dose (2 μg/kg) clonidine, and after high-dose (5 μg/kg) clonidine, respectively. In panels A–D, data are expressed as mean ± SE values (n = 8). The smooth curve or the line was drawn using mean values of fitted parameters. In panels E–H, data are expressed as box and whisker plots (n = 8). The box indicates the 25th–75th percentile range. The horizontal line in the box indicates the median. The values above the 75th percentile plus 1.5 times the interquartile range (IQR) or those below the 25th percentile minus 1.5 times IQR are defined as outliers (filled circles). The whiskers indicate the minimum and maximum data points, excluding the outliers. In each plot, the mean of data points was superimposed in a cross symbol. *P < 0.05, **P < 0.01, and…

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  Fig. 3. Baroreflex equilibrium diagrams constructed from fitted neural and peripheral arcs with (A) or without (B) the peripheral effect of clonidine. PX, the exclusion of the peripheral effect. Labels C, L, H denote the data under control conditions, after low-dose (2 μg/kg) clonidine, and after high-dose (5 μg/kg) clonidine, respectively. The operating-point AP was defined as the AP at the intersection point between the neural and peripheral arcs (the left arrowheads). In panel C, the operating-point AP values are expressed as the box and whisker plots (n = 8). The box indicates the 25th–75th percentile range. The horizontal line in the box indicates the median. The whiskers indicate the minimum and maximum data points. The mean of data points was superimposed in a cross symbol. *P < 0.05, **P < 0.01, and ***P < 0.001 by a Tukey test following one-way repeated-measures analysis of variance