Calibration of baroreflex equilibrium diagram based on exogenous pressor agents in chronic heart failure rats

Abstract

A baroreflex equilibrium diagram describes the relation between input pressure and sympathetic nerve activity (SNA) and that between SNA and arterial pressure (AP). To calibrate the SNA axis (abscissa) of the baroreflex equilibrium diagram, the AP response to intravenous bolus injections of phenylephrine (0.2-50 μg/kg) or norepinephrine (NE, 0.02-5 μg/kg) was examined in normal control rats (NC, n = 9) and rats with chronic heart failure (CHF, n = 6). The maximum slope of the dose-effect curve was significantly smaller in the CHF group than in the NC group (57.3 ± 5.2 vs 80.9 ± 6.3 mmHg/decade for phenylephrine, 60.2 ± 7.8 vs 80.4 ± 5.9 mmHg/decade for NE; P < 0.01). The CHF/NC ratio of the maximum slope was used to calibrate SNA. While the calibrated baroreflex equilibrium diagram showed increased maximum SNA and operating-point SNA in CHF rats compared with NC rats, the magnitude of increase was smaller than that expected from the excess plasma NE concentration in CHF rats. Plasma NE concentration in the CHF group could be disproportionally high relative to SNA.

Keywords: arterial pressure; carotid sinus baroreflex; norepinephrine; open-loop analysis; phenylephrine.

Figure 1

(A) Schematic diagram of the closed-loop negative feedback operation between neural and peripheral arcs of the arterial baroreflex. (B) Schematic diagram of the open-loop analysis of the baroreflex system. (C) Input–output relationships of the neural and peripheral arcs. Notes: The baroreflex equilibrium diagram is obtained by plotting the neural and peripheral arcs on a pressure–SNA plane. The intersection (open circle) indicates the operating point of the baroreflex control. The dotted arrows indicate the operating-point SNA and AP. Abbreviations: AP, arterial pressure; SNA, sympathetic nerve activity; BRP, baroreceptor pressure.

Figure 2

Time series of 10-second moving averaged signals of arterial pressure (AP) in response to intravenous injections of saline and 0.5-, 5-, and 50-μg/kg phenylephrine (PE) injections averaged for the normal control group (NC, n = 9, top panel) and for the chronic heart failure group (CHF, n = 6, bottom panel). Note: Black and gray lines indicate mean values and mean ± standard error values.

Figure 3

Time series of 10-second moving averaged signals of arterial pressure (AP) in response to intravenous injections of saline and 0.05-, 0.5-, and 5-μg/kg norepinephrine (NE) injections averaged for the normal control group (NC, n = 8, top panel) and for the chronic heart failure group (CHF, n = 5, bottom panel). Note: Black and gray lines indicate mean values and mean ± standard error values.

Figure 4

(A) Relation between the dose of phenylephrine and the peak arterial pressure (AP) response. (B) Relation between the dose of norepinephrine and the peak AP response. Data points represent means and standard errors. Smooth curves represent four-parameter logistic functions derived from the mean data points in each group. Abbreviations: NC, normal control; CHF, chronic heart failure; iv, intravenous administration.

Figure 5

(A) Baroreflex equilibrium diagrams of normal control (NC) and chronic heart failure (CHF) constructed using mean parameter values of the neural and peripheral arcs in our previous study. In the neural arc of NC, the response range of SNA is 66.2%, the slope coefficient is 0.13 mmHg⁻¹, the midpoint input pressure is 130.8 mmHg, and the lower plateau of SNA is 39.4%. In the peripheral arc of NC, the slope is 1.03 mmHg/% and the intercept is 29.3 mmHg. In the neural arc of CHF, the response range is 33.1%, the slope coefficient is 0.16 mmHg⁻¹, the midpoint input pressure is 118.1 mmHg, and the lower plateau of SNA is 69.2%. In the peripheral arc of CHF, the slope is 0.78 mmHg/% and the intercept is 37.5 mmHg. (B) Baroreflex equilibrium diagrams of NC and CHF when the SNA axis for the CHF group was scaled so that the slope of the peripheral arc in CHF relative to that in NC became 0.6. Notes: Solid arrows indicate the operating point in NC. Dashed arrows indicate the operating point in CHF. Abbreviations: AP, arterial pressure; au, arbitrary units; BRP, baroreceptor pressure; SNA, sympathetic nerve activity.